Marine natural products

Contents

• 1 Introduction

• 2 Reviews

• 3 Marine microorganisms and phytoplankton
  • 3.1 Marine-sourced bacteria
  • 3.2 Marine-sourced fungi (excluding from mangroves)
  • 3.3 Fungi from mangroves
  • 3.4 Cyanobacteria
  • 3.5 Dinoflagellates

• 4 Green algae

• 5 Brown algae

• 6 Red algae

• 7 Sponges

• 8 Cnidarians

• 9 Bryozoans

• 10 Molluscs

• 11 Tunicates (ascidians)

• 12 Echinoderms

• 13 Mangroves

• 14 Miscellaneous

• 15 Conclusion

• Acknowledgements

• References

---

Abstract

Covering: 2015. Previous review: Nat. Prod. Rep., 2016, 33, 382–431

This review covers the literature published in 2015 for marine natural products (MNPs), with 1220 citations (792 for the period January to December 2015) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1340 in 429 papers for 2015), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

---

John W. Blunt

John Blunt obtained his BSc (Hons) and PhD degrees from the University of Canterbury, followed by postdoctoral appointments in Biochemistry at the University of Wisconsin–Madison, and with Sir Ewart Jones at Oxford University. He took up a lectureship at the University of Canterbury in 1970, from where he retired as an Emeritus Professor in 2008. His research interests are with natural products, the application of NMR techniques to structural problems, and the construction of databases to facilitate natural product investigations.

Brent R. Copp

Brent Copp received his BSc (Hons) and PhD degrees from the University of Canterbury, where he studied the isolation, structure elucidation and structure–activity relationships of biologically active marine natural products under the guidance of Professors Blunt and Munro. He undertook postdoctoral research with Jon Clardy at Cornell and Chris Ireland at the University of Utah. 1992–93 was spent working in industry as an isolation chemist with Xenova Plc, before returning to New Zealand to take a lectureship at the University of Auckland, where he is currently an Associate Professor.

Robert A. Keyzers

Rob Keyzers carried out his BSc (Hons) and PhD studies at Victoria University of Wellington. His thesis research, carried out under the guidance of Assoc. Prof. Peter Northcote, a former contributor to this review, focused on spectroscopy-guided isolation of sponge metabolites. He then carried out post-doctoral research with Mike Davies-Coleman (Rhodes University, South Africa) and Raymond Andersen (University of British Columbia, Canada) before a short role as a flavour and aroma chemist at CSIRO in Adelaide, Australia. He was appointed to the faculty at his alma mater in 2009 where he is currently a Senior Lecturer.

Murray H. G. Munro

Murray Munro, Emeritus Professor in Chemistry at the University of Canterbury, has worked on natural products right through his career. This started with diterpenoids (PhD; Peter Grant, University of Otago), followed by alkaloids during a postdoctoral spell with Alan Battersby at Liverpool. A sabbatical with Ken Rinehart at the University of Illinois in 1973 led to an interest in marine natural products with a particular focus on bioactive compounds which has continued to this day. In recent years his research interests have widened to include terrestrial/marine fungi and actinomycetes.

Michèle R. Prinsep

Michèle Prinsep received her BSc (Hons) and PhD degrees from the University of Canterbury, where she studied the isolation and structural elucidation of biologically active secondary metabolites from sponges and bryozoans under the supervision of Professors Blunt and Munro. She undertook postdoctoral research on cyanobacteria with Richard Moore at the University of Hawaii before returning to New Zealand to take up a lectureship at the University of Waikato, where she is currently an Associate Professor.

---

1 Introduction

This review is of the literature for 2015 and describes 1340 new compounds from 429 papers, a small reduction from the 1378 new compounds in 456 papers reported for 2014.¹ As in previous reviews, the structures are shown only for new compounds, or for previously reported compounds where there has been a structural revision or a newly established stereochemistry. Previously reported compounds for which first syntheses or new bioactivities are described are referenced, but separate structures are generally not shown. Where the absolute configuration has been determined for all stereocentres in a compound, the identifying diagram number is distinguished by addition of the † symbol. The new format for this review introduced for the previous review¹ has been retained, with only a selection of highlighted structures (197) now shown in the review. Compound numbers for structures not highlighted in the review are italicised, and all structures are available for viewing, along with their names, taxonomic origins, locations for collections, and biological activities, in a ESI† document associated with this review. The Reviews section (2) contains selected highlighted reviews, with all other reviews referenced in a section of the ESI.† It is with great regret that we note the passing of Professor Tatsuo Higa, University of the Ryukyus and the Open University of Japan, on May 24 2016. Since 1965 Professor Higa has made many publications of his work, principally on MNPs. Most notable was his discovery of the manzamines. He was a regular participant at MNP conferences, and his quiet and friendly manner will be remembered and missed.

2 Reviews

For 2015 there has been an increase (23% from 2014) in the number of reviews of various aspects of MNP studies. Some of the comprehensive reviews (23) are given here while a listing of the remainder (84) is given in the ESI† section. A full review of MNPs reported in 2013 has appeared.² A statistical analysis of bioactive MNPs discovered from 1985 to 2012 has been made.³ The potential for MNPs as antiviral agents has been extensively reviewed.⁴ Marine fungi as the source of anticancer agents,⁵ antimicrobial compounds⁶ and antiviral agents⁷ have been described. There have been surveys of anticancer compounds from marine sponges⁸ and microalgae,⁹ while the bioactivities of specific classes of MNPs such as peptides,^10,11 polyacetylenes,¹² indole alkaloids,¹³ and halogenated compounds¹⁴ have been reviewed. More specific types of bioactivity have been examined in reviews of MNPs for management of diabetes from seaweeds,¹⁵ and compounds with neuroprotective activity¹⁶ and antifouling properties.¹⁷ MNPs from marine cyanobacteria¹⁸ and actinomycetes of the genus Salinispora¹⁹ have been discussed. The role of metagenomics in biodiscovery continues to develop as described in two new reviews.^20,21 Other emerging concepts for enhancing the biodiscovery effort,²² and recent advances in other experimental technologies,²³ have been described. The online database MarinLit²⁴ continues to be updated and has been the principal source of information for this review.

3 Marine microorganisms and phytoplankton

3.1 Marine-sourced bacteria

Although the first paper in this section adds no new compounds to the list of MNPs it touches on a vital thread running right through the chemistry of MNPs. That is the discovery, characterisation, synthesis, development and commercial production of chemotherapeutic compounds. Endosymbiotic origins of ET-743 (Yondelis^®, trabectedin), isolated from the mangrove tunicate Ecteinascidia turbinata, have long been postulated. From analysis of the metagenomic DNA isolated from the tunicate the complete genome of Candidatus Endoecteinascidia frumentensis, the ET-743 producer, has now been assembled. Analysis of the phylogenetic markers and protein coding genes suggest that Ca. E. frumentensis belongs to a novel family of the γ-proteobacteria. This better understanding of the biosynthesis of ET-743 will promote efforts to produce the drug directly by in vitro methods or heterologous expression rather than the current semi-synthetic process starting from cyanosafracin.²⁵ By utilising low-nutrient conditions and long incubation times 20 previously uncultured species of Gram-negative bacteria were isolated from a variety of marine sources. These species represent new families in the phyla Bacteroidetes and Proteobacteria and include clades that had only been observed before under culture-independent conditions. In the subsequent chemical studies on two species from the new families, Mooreiaceae and Catalimonadaceae, nine new structures were characterised, some with antibiotic properties. From the type strain CNX-216^T (Mooreiaceae) the marinazepinones A 1 and B 2, the marinoaziridines A 3 and B 4, and the marinoquinolines G–I 5–7 were isolated, while CNU-194^T (Catalimonadaceae) and CNX-216^T both produced the marinopyrazinones A 8 and B 9.²⁶

This is the first occurrence of azepin-3-one alkaloids in nature and also the first occurrence of aziridine- and pyrazinone-based alkaloids in Gram-negative bacteria. Two new peptaibols 10 and 11 were isolated from Microbacterium sediminis and is the first reported isolation of peptaibols from an actinomycete, not a fungal source.²⁷ Following the discovery of an antitrypanosomal series of macrolactams the genome of the producing Micromonospora sp. was sequenced and the responsible biosynthetic gene cluster (BGC) identified. By a combination of spectroscopy and sequence data the structures and absolute configurations of the lobosamides A–C 12–14 were established.²⁸ In a neat twist the BGC was assembled as a query sequence and used to identify similar BGCs in other organisms that have been sequenced, but not chemically annotated. By this process the grass-derived Actinomycete, Actinosynnema mirum ATCC 29888,²⁹ was shown to contain a highly similar BGC. Consequent work led to the isolation and characterisation of the non-MNP mirilactams A 15 and B 16, confirming the validity and usefulness of this approach to genome-mining.²⁸

The putative BGC for the fluostatins from Micromonospora rosaria³⁰ was expressed heterologously in Streptomyces coelicolor and led to the isolation of fluostatin L 17 and a fluostatin heterodimer 18,³¹ while investigation of another Micromonospora sp. resulted in isolation of a pimarane derivative 19.³² Based on Micromonosporaceae spp. the parameters for induced biosynthesis by interspecies interaction in co-culture were explored using a micro-scale approach and LC/MS-PCA methods to assess secondary metabolite production.³³ Aminoimidazoles 20 and 21,³⁴ diketopiperazines 22 (ref. 35) and 23 (ref. 36) (new to marine)³⁷ and dimeric indoles 24 and 25 (ref. 38) were reported from Norcadiopsis and Rubrobacter spp. Work on the actinomycete Saccharothrix sp. led to the isolation of further aromatic polyketides saccharothrixones A–D 26–29, new members of the tetracenomycin (Tcm) family. Saccharothrixone D is unusual in that it has the opposite chirality to Tcm C at each stereocentre.³⁹

Another innovative genome-mining approach is pattern-based and employs molecular networking. This approach was applied to 35 Salinospora samples across the three defined species. 30 Draft genome sequences were known. Cultures were grown under standard conditions to the commencement of stationary phase growth. Analysis of the extracts by HRMS/MS generated over 200 000 spectra, which in turn generated 1137 parent ion nodes. Seeding this Salinospora molecular network with previously identified Salinospora sp. compounds allowed identification of known compounds, possible media components and new derivatives of known compounds (methylation, hydroxylation, etc.). Molecular networking coupled with genome sequence data allowed for the rapid correlation between a BGC and the resultant secondary metabolite (pattern-generation). In this example it was found that the cluster NPRS40 was unique to one strain. Peptidogenomics was used to correlate this BGC with the 1171.42 Da parent ion node which in turn led to the characterisation of retimycin A 30, a new quinomycin-like depsipeptide.⁴⁰ Sioxanthin 31, an unusual carotenoid in that it is glycosylated at one end with an aryl group at the other end, is the pigment responsible for the distinctive orange coloration of Salinospora spp. during vegetative growth. The biosynthesis of sioxanthin is also unusual as the carotenoid biosynthesis genes are non-clustered in the Salinospora genomes.⁴¹

The first successful heterologous expression of a gene cluster from the Salinospora genome has been made. An 18kb type II PKS gene cluster from S. pacifica with high homology to the enterocin locus in Streptomyces maritimus was transferred to S. coelicolor M1146 and S. lividans TK23. Both clones produced enterocin. This opens the way to further explore the cryptic pathways of the Salinospora's secondary metabolome.⁴² From the screening of a pre-fractionated library of marine bacterial-derived extracts against Plasmodium falciparum (P. falciparum) a new class of antimalarials was discovered from a Salinospora sp. The salinipostins A–K 32–42 are long-chain bicyclic phosphotriesters, a rarely observed natural product scaffold. VCD (Vibrational CD spectroscopy) was used to establish configuration in the series as (S_P, S_C). The potency against P. falciparum ranged over three orders of magnitude (0.05 μM to 46 μM) varying with the length of R₁ and R₂: salinipostin A 32 was the most potent. In contrast, the salinipostins were relatively non-toxic to mammalian cells (>50 μM). Encouragingly, initial attempts to select for resistance in P. falciparum were not successful.⁴³

Also in the antimalarial area was the quantitative high throughput screening of another large natural products library (16 503 extracts) across four orders of magnitude in concentration against six geographically different strains of P. falciparum which identified two Streptomyces spp. for further investigation. Each contained a similar suite of compounds so only S. bangulaensis was explored further. The recently identified actinoramide A/pandanamide A^44,45 was the major metabolite along with three new analogues actinoramide D–F 43–45.⁴⁶

Another major screening effort was against >33 000 extracts from 5036 cultivatable Costa Rican marine microorganisms to discover activators of the apoptotic arm of unfolded protein response (UPR). High levels of UPR signaling characterize many human cancers. The screening led to the discovery of three further lobophorin^47–50 congeners 46, 47 and 48 from a Streptomyces sp. and, subject to supply, further studies will examine the mechanism by which active lobophorins activate UPR.⁵¹

The gene cluster for the anti-infective desotamides from S. scopuliridis has been identified and after heterologous expression in S. lividans and S. coelicolor the desotamide congener G 49 was characterized.⁵² A further depsipeptide in the salinamide series, F 50, was isolated from re-cultivation of Streptomyces sp. CNB-091.⁵³ To address the bottleneck that often impedes progress in research, 3D-NMR techniques have been applied to the structure determination of peptidic natural products of interest. To balance costs, yield and relative ¹³C/¹⁵N abundance the growth media used peptone and yeast extract and ¹⁵NH₄Cl and [U-¹³C]-glucose. The Streptomyces sp., isolated from Eudistoma olivaceum was fermented in this media and the two peptides under study, eudistamides A 51 and B 52, were isolated. Seven of the typical protein triple resonance experiments were evaluated. Of these HNCO, CBCANH and CBCA(CO)NH were used to establish the peptide backbone and HCCH-TOCSY was most useful for side-chain assignments. The absolute configurations were assigned by traditional methods. It was concluded that this approach is cost effective and greatly improves the confidence in a proposed structure.⁵⁴

New ansamycin analogues 53–55 were obtained from a mutant strain of S. seoulensis,⁵⁵ and further ikarugamycin⁵⁶ derivatives (tetramic acid macrolactams) 56–58 were isolated from a S. zhaozhouensis.⁵⁷ A combination of gene inactivation and complementation, synthetic substrates and extensive phylogenetic tree analyses revealed that tetramic acid and pyridone biosynthesis proceeds via a series of Dieckmann cyclases.⁵⁸ A new analogue of the dilactone echinomycin 59 was characterized from a Streptomyces sp. along with a new diketopiperazine 60.⁵⁹ Another macrolide in the bafilomycin family 61, was produced by a Streptomyces sp. isolated from litter at a river mouth.⁶⁰ Following genetic manipulation of a marine Streptomyces olivaceus by disruption of orf-1741, a putative transcriptional gene, three halogenated dibenzoxazapinone derivatives, the mycemycins C–E 62–64, were isolated from the mutant strain and are the first dibenzoxazapinones produced from a microbial source.⁶¹

Marine Actinobacteria continue to surprise with the versatility of their biosynthetic machinery. Phylogenetic studies have led to the identification of 13 distinct marine actinomycete groups. The chemical investigation from one of these groups, a member of the family Streptomycetaceae, led to the isolation of two new classes of marine alkaloid, represented by actinobenzoquinoline 65, and the actinophenanthrolines A–C 66–68. Both these new classes are unprecedented in the alkaloid literature. Structural proof relied heavily on long-range gHMBC and was supported by X-ray diffraction analysis.⁶²

Further bohemamine derivatives 69 and 70,⁶³ two epimeric benzofurans 71 and 72,⁶⁴ ten angucyclinone derivatives 73 and 74,⁶⁵75–82,⁶⁶ anthracyclines 83 and 84 (ref. 67) a naphthacene glycoside 85 (ref. 68) (new to marine) and a further aureolic acid 86 (ref. 69) were isolated from sedimentary or endophytic Streptomyces spp. A strategy for containing HIV is reactivation of the latent virus in combination with HAART. In the search for reactivators a 5000 strong microbially-derived pre-fractionated natural product library was screened against a model of in vitro HIV latency in human CD4⁺ T cells. Selected pre-fractions were subjected to LC/MS fractionation and re-assayed. This identified a series of abyssomicin⁷⁰ congeners 1–5 87–91 as the optimal leads. Of these, abyssomicin 2 88, was prioritised based on its robust reactivating activity. Abyssomicin 2 appeared to be identical with a synthetic derivative of abyssomicin I,⁷¹ but further examination revealed that abyssomicin 2 88 was enantiomeric with the synthetic derivative as the absolute configuration of abyssomicin I had been incorrectly assigned. In this process the structure of abyssomicin I was also reassigned as abyssomicin 1 87. The mechanism of reactivation by the abyssomicins remains to be elucidated.⁷²

A number of other compounds of lower molecular weight were also isolated from actinomyctes or Streptomyces spp. These included two butenolides 92 and 93,⁷³ four cycloheximide derivatives 94–97,⁷⁴ a furanone 98,⁷⁵ an α-pyrone 99,⁷⁶ four benzothioate glycosides 100–103,⁷⁷ an alkylamide 104,⁷⁸ an aniline derivative 105 with algicidal properties⁷⁹ and an incompletely characterized cyslabdan-like compound 106.⁸⁰ Anti-dormant mycobacterial properties were reported for the known terrestrial antibiotic nybomycin⁸¹ isolated, in this instance, from a marine Streptomycete. This is the first report of nybomycin from a marine source.⁸² The biodiversity of the Yellow Sea was explored with sediment samples collected from five locations between 50–100 m. Culturing led to the isolation of 613 actinomycete samples of which 89 species were shown to produce extracts with good antimicrobial properties against an array of microorganisms. Of these 76 were Streptomyces spp. while the remaining 12 split across four genera (Kocaria, Micromonospora, Nocardiopsis, Saccharomonospora). After 16S rRNA gene analysis the Streptomyces spp. could be split into 17 clades. This survey indicated that this previously under-explored ocean contains a wealth of microbial potential. One of the Streptomyces species further explored produced three diketopiperazine dimers, including the new dimer isonaseseazine B 107, a stereoisomer of naseseazine B.^83,84

A modified diketopiperazine 108 with antimalarial properties was isolated from a Streptomyces sp. isolate from the Florida Keys as part of the outcome of screening a large collection of microorganisms for antiproliferative and antiplasmodial properties.⁸⁵ There were three reports of new compounds from the phylum Firmicutes. These covered the isolation of new glycolipids 109 and 110 from a sediment-derived Bacillus licheniformis,⁸⁶ and two lipopeptides 111 and 112 that differ only in the chain-length of the 3-hydroxy fatty acid.⁸⁷ A cyclic tetrapeptide 113 was isolated from the culture broth of a Staphylococcus sp.⁸⁸ A number of papers reported new compounds from the phylum Proteobacteria. An imaging mass spectrometry and molecular networking approach led to the discovery of the vitroprocines A–J 114–123. Selective assaying reduced the 265 marine-derived microorganisms from the Taiwan Strait to a single Vibrio sp. active against Acinetobacter baumanni. Imaging mass spectrometry on the intact organism was used to determine the mass range of the metabolites and concluded from the spatial distribution that they were secretory in nature and matched the data from LC/MS analysis of the crude EtOAc extract of the Vibrio sp. Molecular networking analysis generated three clusters of 43 nodes of which 31 could be differentiated into seven sub-groups. The molecular masses in these sub-groups did not correspond to known microbial products (MarinLit,²⁴ AntiBase⁸⁹). Of the 10 vitroprocines subsequently isolated, vitoprocines A–C 114–116 were most active against A. baumanni.⁹⁰

A series of known depsipeptides, kailuin B–F 124–128, and two new analogues kailuin G 129 and H 130 were isolated from Photobacterium halotolerans. During this study the double bond configuration of kailuin D 126 was corrected and the previously unreported configuration at C-3 of the β-acyloxy grouping of all of the kailuins 124–126 and 129–131 assigned using a combination of Mosher's chemistry and α, β, γ ¹³C-NMR shifts. It was suggested that as the kailuins had previously been isolated from Vibrio spp., which predated the description of the type strain for Photobacterium halotolerans, revisiting the taxonomy might be in order.⁹¹

A new siderophore 132 and pre-pseudomonine 133 (new to marine) were isolated from a sponge-associated Pseudomonas fluorescens.⁹² The primary structure of a capsular polysaccharide from the Arctic psychrophilic bacterium Colwellia psychrerythraea has been defined from extensive NMR studies and chemical analysis and was reported as a repeating tetrasaccharide unit comprising two amino sugars, two uronic acids and a threonine substituent, 134.⁹³

The seashore Actinobacteria derived from mangroves, sea-grasses, salterns and mud-flats have been grouped separately on the grounds that as a group they have been exposed to much greater changes in temperature, submersion, salinity and sunlight than their oceanic counterparts. Following isolation of a series of the polycyclic xiamycin⁹⁴ and other indolesesquiterpenes⁹⁵ from mangrove Streptomyces sp. endophytes the xiamycin biosynthetic gene cluster was successfully transferred to S. griseus. From the recombinant strain three minor, sulfonyl-bridged dimeric congeners sulfadixiamycin A–C 135–137 were isolated. From a biosynthetic perspective a sulfonyl-linkage is unusual and it was postulated that a direct flavin-mediated SO₂ incorporation was involved.⁹⁶ Other aspects of the biosynthesis of the xiamycins and the cyclisation cascades were elucidated by the biomimetic synthesis of key intermediates.⁹⁷

Two other endophytic Streptomyces spp., also obtained from the stem of the mangrove Bruguiera gymnorrhiza, led to three bacterial caryolanes bacaryolane A–C 138–140. These are mirror images of typical plant-derived caryolanes.⁹⁸ The other Streptomyces sp. endophyte yielded a series of divergolide⁹⁹ congeners 141–146.¹⁰⁰ A thiazine 147 and two thiazoles 148 and 149 were isolated from a mangrove sediment-derived Actinomycetospora chlora. This is the first reported natural occurrence of a 5-hydroxy-3-phenyl-4H-1,3-thiazine-4-one core.¹⁰¹

Derived from mangrove sediment-sourced actinomycetes were 150 (ref. 102) and preQ₀,¹⁰³151 (first-time natural product)¹⁰⁴ while 152–154 came from an endophyte of the sea-grass Salicornia sp.¹⁰⁵ A tidal mud-flat Streptomyces sp. was the source of the hormaomycins B 155 and C 156, which each contain the unusual structural features (4Z)-propenyl-proline, 3-(2-nitrocyclopropyl)-alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and 3-methylphenylalanine only found before in hormaomycin.^106,107

A further mud-flat Streptomycete produced the dilactone-tethered, pseudo-dimeric peptides mohangamide A 157 and B 158. Apart from the dilactone-tethering, another interesting feature of these metabolites was the acyl chain-bearing dihydropyridine. A four-step derivatisation approach was used to determine the absolute configuration at C-62 of mohangamide A 157.¹⁰⁸ Also isolated from a tidal mud-flat or saltern Streptomyces sp. were 159, 160 (ref. 109) and 161–165,^110,111 while the salinazinones A 166 and B 167 are first examples of a natural alkaloid with an oxazinone-pyrrolidione core.¹¹²

A number of successful synthetic and biosynthetic studies have been realised. These included peptide-based targets such as marthiapeptide,^113,114 the disulfide-containing peptide thiochondrilline C,^115,116 bogorol A and the more thermodynamically-favoured (Z) isomer,^117,118 the siderophores amphibactin-T¹¹⁹ and moanachelin ala-B.^120,121 The first synthesis of fradcarbazole¹²² was by semi-synthesis¹²³ from staurosporine.¹²⁴ Also successfully synthesised were the nitrosporeusines,^125,126 fijiolide A,^127,128 marinisporolide^129,130 and splenocin B.^131,132 A new route to isoquinolines was developed for the synthesis of mansouramycin^133,134 and a total synthesis and full stereochemical assignments have been completed for heronapyrroles A 168 and B 169.^135,136 A further synthesis of bacillamide B¹³⁷ has reconfirmed the absolute configuration as (S) and that the specific optical rotation is negative.¹³⁸ The unusual anthracycline marmoycin¹³⁹ has been successfully synthesised and fluorescent microscopy studies indicated that it accumulates in the lysosomes and not the cell nucleus.¹⁴⁰ The synthesis of immunoaffinity fluorescent probes of chlorizidine A¹⁴¹ established that two cystolic proteins, part of the glycolytic cycle, were the targets for chlorizidine,¹⁴² while studies on the mechanism of action of thalassospiramides¹⁴³ confirmed that the nanomolar activity of this group of lipopeptides against human calpain 1 protease can be ascribed to the rigid 12-membered ring containing the α,β-unsaturated amide moiety that is conserved across the group.¹⁴⁴ Annotations of the draft genome sequence of the Streptomyces sp. producing akaeolide¹⁴⁵ and lorneic acid¹⁴⁶ identified type 1 PKS clusters and the PKS origins were supported by ¹³C-labeling studies.¹⁴⁷ The biosynthetic gene cluster for the production of the marformycins,¹⁴⁸mfn, has been identified from Streptomyces drozdowiczi and encodes six NRPS's and related proteins for the assembly of the depsipeptide core structure.¹⁴⁹ Two papers addressed heronamide¹⁵⁰ biosynthesis. Firstly, the gene cluster for heronamide F was identified from a deep-sea Streptomyces sp. and the presence of a β,γ-migrated diene system in the side-chain confirmed by ¹³C-labeling studies.¹⁵¹ The second paper was a theoretical examination of the proposed transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of heronamide A. The DFT computational results support that proposal and suggest that the cycloaddition is highly stereoselective giving one product, but proceeds via a ambimodal transition state that can lead to both the observed [6 + 4] and unobserved [4 + 2] products with the [4 + 2] product being less stable (5.2 kcal mol⁻¹).¹⁵² Structurally, anthracimycin and chlorotonil are virtually identical but were isolated from a Streptomyces sp.^153,154 and Sorangium cellulosum,¹⁵⁵ a myxobacterium, respectively. Chlorotonil differs from anthracimycin in that all sp³ stereocenters are inverted, there is an additional methyl group and a gem-dichloro entity. The two biosynthetic gene clusters have been compared in two papers published side-by-side. Both compounds are formed by trans-AT PKS pathways and clusters in the chlorotonil genome readily explain the chlorination and methylation pattern. In each case the decalin ring system is formed by a spontaneous [4 + 2] cycloaddition and it is proposed that the alternative stereochemistries are in part a consequence of the orientation of the C16 methyl group pre-organising the PKS-bound intermediate prior to the [4 + 2] cycloaddition.^156,157 The biosynthesis of two similar Salinispora pacifica metabolites, salinipyrone and pacificanone,¹⁵⁸ was unexpectedly correlated with the large PKS cluster from Micromonospora carbonacea¹⁵⁹ that produces the macrolide rosamicin¹⁶⁰ and illustrates how domain and module skipping can give rise to polyketide product diversity.¹⁶¹ From a study of splenocin¹³¹ biosynthesis the new aromatic CoA-linked extender unit, benzylmalonyl-CoA, was identified and provides a link between amino acid and CoA-linked extender units and opens access to the bio-engineering of polyketide carbon scaffolds.¹⁶² To reach the conclusion that indole-C-3 methylation of cyclo-L-Trp-L-Trp precedes indole-C-3′ prenylation and transfer of a second methyl to the N′ position in the biosynthesis of the nocardioazine alkaloids¹⁶³ required bioinformatics analysis, bioinspired syntheses and MS metabolomics profiling.¹⁶⁴ Target-directed genome mining is a new strategy for the discovery of new biosynthetic pathways and the concept was developed around an analysis of the pan-genome of 86 Salinospora bacterial genomes. The strategy operates by querying the genomes for duplicated housekeeping genes that are co-localised with biosynthetic gene clusters.¹⁶⁵ The initial development of cytological screening of natural product extracts using a high content imaging approach to generate phenotype fingerprints has been extended from the original 312 extracts¹⁶⁶ to over 5000 pre-fractionated extracts from marine Actinobacteria and demonstrated the role that untargeted cytological screening can play in ascertaining the pathways and the mechanisms disrupted and so leading to a targeted selection of extracts based on a potential mode of action.¹⁶⁷

3.2 Marine-sourced fungi (excluding from mangroves)

Studies of fungi continue to be on the rise with 371 new compounds reported in 2015 compared to 318 in 2014 and 223 in 2013. A number of new metabolites have been obtained from the genera Acremonium (benzophenones 170–172 (ref. 168)), Alternaria (tricycloalternarenes 173 and 174,¹⁶⁹ and a spiro decalin derivative 175 (ref. 170)), Arthirinium (alkaloids 176–178 (ref. 171) and cytochalasins 179–183).¹⁷² Of these, arthrinium A 179 was claimed as new but is a known natural product derivative¹⁷³ and ketocytochalasin 183 (ref. 173) is a first time MNP.¹⁷² Citromycetin analogue 184 was obtained from an Ascomyta sp.,¹⁷⁴ while as usual, the genus Aspergillus has been well studied. Of particular note was a continuing study into the biosynthesis of the prenylated indole alkaloids notoamides,¹⁷⁵ stephacidins¹⁷⁶ and versicolamide B.¹⁷⁷ Feeding of [¹³C]₂ racemic 6-epi-notoamide T¹⁷⁸ to Aspergillus sp.¹⁷⁹ cultured in liquid media resulted in incorporation into versicolamide B and also into seven new metabolites 185–191, which were not produced under normal culture conditions. The same incorporation experiment on agar medium resulted in production of four additional new metabolites, 192–195. All were produced as racemic mixtures. It was suggested that addition of excess precursor to the cultures activated expression of dormant tailoring genes.¹⁸⁰

Other metabolites produced by Aspergillus species included spiculisporic acid analogues 196 and 197,¹⁸¹ phenyl ether derivatives 198–202, of which dehydrocyclopeptine¹⁸²201 and viridicatin¹⁸²202 were obtained as first time MNPs,¹⁸³ polyketide 203 and decaline derivative 204,¹⁸⁴ alkaloids 205–207,¹⁸⁵208–210,¹⁸⁶ indole diterpenoids 211 and 212,¹⁸⁷ isocoumarin 213, cyclohexapeptide 214 and pyripyropene derivative 215,¹⁸⁸ peptides 216 and 217,¹⁸⁹218,¹⁹⁰ hydroxyphenylacetic acid derivative 219,¹⁹¹ alkaloids 220 (also synthesised)¹⁹² and 221–225,¹⁹³ the steroids 226, 2-O-methylbutyrolactone I 227 (aspernolide C)¹⁹⁴ and 2-O-methylbutyrolactone II¹⁹⁵228 (last two as new MNPs),¹⁹⁶ meroterpenoids 229–232,¹⁹⁷ alcohols 233–250,¹⁹⁸ alkaloid 251,¹⁹⁹ xanthone 252, alkaloid 253 (ref. 200) and dihydroisocoumarin 254.²⁰¹ The stereochemistry of 5′-hydroxyasperentin²⁰² was established as (3R,10R,13S,14S) 255 by X-ray crystallography.²⁰¹ New metabolites were isolated from the genera Auxarthron (triterpene glycoside 256 (ref. 203)) and Beauveria (co-culture with Penicillium) (citrinin derivatives 257 and 258 (ref. 204)). Several new tetramic acids, chaunolidine A–C 259–261 and a pyridinone, chaunolidone 262 were obtained from an Australian Chaunopycnis sp.²⁰⁵ Additionally, the absolute configuration of the co-isolated tetramic acid F-14329, previously obtained from terrestrial Chaunopycnis²⁰⁶ and Tolypocladium²⁰⁷ species, was established as 263 and is a first time MNP. Chaunolidone 262 possessed selective and potent cytotoxicity to the NCI-H460 cell line.²⁰⁵ Interestingly, compounds with the same planar structures as chaunolidines A 259 and C 261 were simultaneously reported as metabolites of the terrestrial fungus Tolypocladium cylindrosporum.²⁰⁸

An OSMAC approach was utilised in the isolation of polyketides 264 and 265 from Cladosporium sphaerospermum²⁰⁹ and other metabolites obtained from Cladosporium species included diketopiperazines 266 and 267,²¹⁰ bicyclic lactam 268 (ref. 211) and polyketides 269 and 270.²¹² New metabolites isolated from the genera Corynepsora included chromone derivatives 271–282 (ref. 213) while Dichotomomyces spp. produced the thiodiketopiperazines 283–285, (284 (ref. 214) and 285 (ref. 215) as first time MNPs),²¹⁶ and steroids 286–288.²¹⁷ From Emericella spp. the polyketides 289–296 (ref. 218) and lactones 297–300 (ref. 219) were characterised while the isopimarane 301 (ref. 220) came from an Epicoccum sp. and a Eurotium sp. gave the prenylated indole diketopiperazines 302–316.²²¹ The co-isolated alkaloid neoechinulin B^222,223 was shown to be a potent inhibitor of H1N1 virus and a panel of other influenza virus strains through binding to viral hemagglutinin disrupting the attachment of viruses to host cells.²²¹ Further new metabolites were obtained from the genera Gliomastix (macrolides 317–321 (ref. 224)), Graphium (thiodiketopiperazines 322–329,²²⁵330 and 331 (ref. 226)) and Hypocrea (furan derivatives 332, 333 and cyclopentenone derivatives 334–338).²²⁷ Two of these compounds, N-isobutyl-2-phenylacetamide²²⁸337 and N-(2-methylbutyl)-2-phenylacetamide²²⁹338 were first time NPs.²²⁷ New natural products were isolated from the genera Lophiostoma (merosesquiterpenoids craterellin D 339 and craterellin A²³⁰340; first marine isolation for the latter),²³¹ and Nectria (monoterpenoid α-pyrones 341 and 342).²³² Of these, nectriapyrone D²³²342 was simultaneously isolated from a terrestrial fungus as gulpyrone B.²³³ The genera Neosartorya and Paecilomyces also yielded new metabolites (alkaloids 343 and 344,²³⁴ meroditerpene 345 and alkaloids 346 and 347 (ref. 235) and butenolide derivatives 348 and 349,²³⁶ alkaloids 350 and 351,²³⁷352 and 353 (ref. 238) and octaketide spiroketals 354–357 (ref. 239)). The genus Penicillium was, as always, a prolific source of new metabolites, including bisthiodiketopiperazines 358 and 359, sesquiterpenes 360 and 361,²⁴⁰ phenolic bisbolanes 362–364 and nor-bisbolane 365,²⁴¹ benzoic acid derivative 366,²⁴² citrinin derivatives 367–370 and tetramic acid analogues 371 and 372.²⁴³ A culture of P. adametzioides was the source of the dithiodiketopiperazine derivatives peniciadametizine A 373, with the unique spiro[furan-2,7′-pyrazino[1,2-b][1,2]oxazine] skeleton, along with an analogue, peniciadametizine B 374, both inhibitors of the plant pathogenic fungus Alternaria brassicae.²⁴⁴ Penicitrinine A, 375 also with a unique spiro skeleton, was obtained from P. citrinum and was cytotoxic to a wide range of tumour cell lines. It also induced apoptosis and suppressed metastasis.²⁴⁵

Phthalide derivatives 376 (ref. 246) (first time MNP) and 377, isopatulin²⁴⁷378 (first time MNP),²⁴⁸ and oxindole alkaloids 379–386 were also isolated from the Penicillium genus.²⁴⁹ Another oxindole alkaloid 387 was claimed as new and named cyclopiamide I²⁴⁹ but had already been reported in 2014 as aspergilline D.²⁵⁰ The current report does however represent the first marine isolation.²⁴⁹ The gene cluster from Penicillium expansum responsible for biosynthesis of the indole alkaloids communesins²⁵¹ has been identified. In the process, three new metabolites, communesin I–K 388–390 were isolated. The investigation confirmed that communesins originate from L-tryptophan via coupling of tryptamine and aurantioclavine.²⁵²

Further metabolites isolated from the genus Penicillium include meroterpenes 391 and 392,²⁵³ alkaloids 393,²⁵⁴394–396,²⁵⁵ diphenylmethanone derivative 397,²⁵⁶ phenolic enamide 398 and meroterpenoid 399,²⁵⁷ azaphilone derivatives 400–402 and diphenyl ether derivatives 403 and 404.²⁵⁸ The planar structure of 404 appears in a screening library²⁵⁹ but no source is given for the compound. Chromones 405–409,²⁶⁰ sesquiterpenes 410–413,²⁶¹ merosesquiterpenes 414 and 415,²⁶² 1,4-diazepane 416,²⁶³ tanzawaic acids 417–420,²⁶⁴ diketopiperazine 421,²⁶⁵ polyketides 422–426,²⁶⁶ spiroindoline alkaloids 427 and 428,²⁶⁷ and azaphilone derivatives 429 and 430 (ref. 268) were also obtained from Penicillium species. P. vinaceum was the source of penicillivinacine 431, which exhibited potent antimigratory activity against the highly metastatic breast cancer cell line MDA-MB-231.²⁶⁹ A sponge-derived Penicillium sp. yielded the fusarielin analogue 432 when grown axenically but co-culture of this strain with another Penicillium strain obtained from the same sponge elicited production of the known compounds norlichexanthone²⁷⁰ and monocerin²⁷¹433 (first time MNP), neither of which was detected in the individual axenic cultures of the two strains.²⁷²

A soft coral-related Pestalotiopsis sp. was the source of enantiomeric alkaloid dimers (+)- and (−)-pestaloxazine A 434 and 435.²⁷³ These mixed polyketide-cyclopeptide metabolites (PKS-NRPS hybrids) possessed a unique, symmetric spiro[oxazinane-piperazinedione] skeleton and the racemate and each enantiomer exhibited Enterovirus 71 (EV71) activity but 434 was more selective and more potent.²⁷³

The genus Pestalotiopsis yielded a number of other new metabolites, including meroterpenoids 436 and 437, isocoumarin 438, phenol 439 (ref. 274) phthalide derivative 440,²⁷⁵ 5′-O-acetyl uridine²⁷⁶441 (ref. 275) (new NP) and pestarhamnoses A–C 442–444.²⁷⁷ The pestarhamnoses were obtained through cultivation on a modified medium which contained equal concentrations of sodium chloride and potassium bromide in an expectation of producing brominated analogues of the previously isolated pestalachlorides.^278,279 Interestingly, no brominated analogues were detected but pestalachlorides C and D²⁷⁹ were isolated along with pestarhamnoses A–C 442–444.²⁷⁷

Other fungal genera to yield new metabolites included Phaeosphaeria (polyketides 445 and 446),²⁸⁰Phoma (cytochalasin derivatives 447–449, cytochalasin B6 (ref. 281) 450 (first NP isolation)),²⁸²Pleosporales (pleosporalins A–G 451–457),²⁸³Pseudoallescheria (chlorinated benzofurans 458 and 459,²⁸⁴ pseudellones A–C 460–462 (ref. 285)) and Pseudogymnoascus (nitrated asterric acid derivatives 463–466).²⁸⁶ The ascidian-derived Roussoella sp. produced roussoellatide 467, a dichlorinated polyketide with an unprecedented skeleton and experiments with [1-¹³C]-, [2-¹³C]- and [1,2-¹³C]-acetate suggested that biosynthesis proceeds from two pentaketides that each undergo Favorskii rearrangement prior to being joined by an intermolecular Diels–Alder reaction.²⁸⁷

New metabolites were also obtained from the genera Simplicillium (diketopiperazine 468 and furanone²⁸⁸469; the latter a first time MNP²⁸⁹), Spicaria (isobenzofurans as acetylated derivatives 470–473),²⁹⁰Spiromastix (polyphenols 474–484),²⁹¹Stachybotrys (meroterpenoid sulfate 485,²⁹² sesquiterpenoid 486 and xanthone derivatives 487 and 488 (ref. 293)), Talaromyces (sesquiterpene-conjugated amino acids 489–492,²⁹⁴ diphenyl ether derivatives 493–495 and tenellic acid methyl ester (first time MNP)²⁹⁵496,²⁹⁶ oxaphenalenone dimers 497 and 498 and isopentenyl xanthone 499 (ref. 297)) and Trichobotrys (tetramic acid dervatives 500–505).²⁹⁸ A red algal-derived Trichoderma species produced gliovirin,²⁹⁹ pretrichodermamide A³⁰⁰ and the related trichodermamide A³⁰¹ when grown on a freshwater medium, chlorinated derivatives trichodermamide B³⁰¹ and DC1149B³⁰²506 when cultured in natural seawater and a new iodinated derivative 507 (ref. 303) when cultured in a freshwater medium supplemented with sodium iodide. A brominated analogue, DC1149R³⁰²508 was obtained with sodium bromide supplementation to the freshwater medium and isolated for the first time as a natural product.³⁰³ Cultivation of the strain in seawater supplemented with dimethylsulfoxide (DMSO) yielded the trithio-derivative, chlorotrithiobrevamide 509.³⁰⁴ Decalin derivatives 510–512,³⁰⁵ lipids 513–520 (ref. 306) and octaketides 521 and 522 (ref. 307) were also obtained from the genus Trichoderma.

The genus Truncatella was the source of some isoprenylated cyclohexanols 523–536,³⁰⁸ while an antibiotic polyketide 537 and ascosetin³⁰⁹538 were obtained from a fungus of the Lindgomycetaceae family.³¹⁰ Synthesis of the octaketide ascospiroketal A, originally obtained from Ascochyta salicorniae,³¹¹via a Ag^I-promoted cyclisation cascade, revised the stereochemistry to 539 and indicated that the structure of ascospiroketal B³¹¹ should also be revised accordingly.^312,313 Remisporine A was originally obtained from Remispora maritima and spontaneously dimerises to form remisporine B.³¹⁴ Comparison of the calculated and measured ECD spectra of remisporine B suggested a revision of configuration. By extension the configuration of natural product remisporine A should be changed to 540.³¹⁵ The structure of trichodermatide A, originally obtained from Trichoderma reesei,³¹⁶ has been revised to 541, a C-10 epimer of the structure originally proposed via synthesis and X-ray structure analysis of a synthetic intermediate of trichodermatide A.³¹⁷ Total synthesis of the proposed structure of the cyclic hexapeptide similanamide, obtained from Aspergillus similanensis associated with the sponge Rhabdermia sp.¹⁸⁸ and comparison of the NMR data of the synthetic compound with those of the natural product, has indicated that similanamide is in fact identical to PF1171C,³¹⁸ a hexapeptide previously obtained from an unidentified soil ascomycete.³¹⁹Clonostachys rosea was the source of a new natural product, 4-methyl-(6E,8E)-hexadecadienoic acid 542, previously known only from methanolysis of a metabolite of the mushroom Microporellus subsessilis.³²⁰ This fatty acid inhibited growth of MCF-7 cells and down-regulated the lipogenic enzymes acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS).³²¹ Acetylgliotoxin G³²²543 was obtained for the first time as a MNP as was the known synthetic open-chain hemisuccinimide 544,³²³ (Penicillium copticola) which was named penicillimide.³²⁴ Alternariol-9-methyl ether 3-O-sulfate 545, previously obtained from Alternaria sp., an endophyte of the Egyptian medicinal plant Polygonum senegalense,³²⁵ was obtained for the first time from the marine environment from endophytic Alternaria alternata.³²⁶ The norditerpenes aspewentin A–C (Aspergillus wentii³²⁷) have been synthesised³²⁸ as have the prenylated indole alkaloids, (+)-notoamide I (Aspergillus sp.)³²⁹ and (−)-17-hydroxy-citrinalin B (Penicillium citrinum)³³⁰via a unified strategy.³³¹ Herbarins A and B originally obtained from Cladosporium herbarum³³² have been synthesised via a multi-step procedure and both displayed antioxidant properties.³³³ Starting from the sugar D-lyxose, total synthesis of cochliomycin C^334,335 has been achieved.³³⁶ Total synthesis of the macrolide dendrodolide K³³⁷ (Dendrodochium sp.) has been accomplished from a commercially available substrate by a convergent strategy³³⁸ and other dendrolides (F, G, I, J and L³³⁷) have also been synthesised via a unified strategy employing ring-closing metathesis.³³⁹ A unified strategy was also employed in the total synthesis of luteoalbusins A and B,³⁴⁰ indole diketopiperazines isolated from sediment-derived Acrostalagmus luteoalbus.³⁴¹ In addition to the new compound talaromycin C,²⁹⁶ purpactins A,³⁴² C³⁴² and penicillide³⁴³ exhibited potent antifouling activity against settlement of Balanus amphitrite larvae²⁹⁶ as did altertoxin I, a metabolite of both terrestrial³⁴⁴ and marine³⁴⁵Alternaria alternata.³⁴⁶ A number of known cyclic dipeptides, cyclo(Gly-L-Pro),³⁴⁷ cyclo(L-Ala-L-Pro),³⁴⁸ cyclo(D-Ala-L-Pro),³⁴⁹ cyclo(L-4-Hyp-L-Pro)³⁵⁰ and cyclo(L-Hyp-D-Phe)³⁵¹ were reisolated from Eupenicillium brefeldianum and induced extracellular alkalinisation and hydrogen peroxide production in plant cell suspensions, indicating their potential as induced systemic resistance (ISR) elicitors.³⁵² Viridicatol, a metabolite of Aspergillus versicolor,³⁵³ has been obtained from Penicillium sp. as an antiinflammatory agent, inhibiting the nuclear factor-kappa B (NF-κB) pathway in LPS-stimulated RAW264.7 and BV2 cells.³⁵⁴ Spiromastixones are chlorodepsidone metabolites of Spiromastix sp.³⁵⁵ which strongly inhibit cholesterol uptake and stimulate cholesterol efflux to apolipoprotein A1 (ApoA1) and high-density lipoprotein (HDL) in RAW264.7 macrophages.³⁵⁶ FGFC1 (fungi fibrinolytic compound 1),³⁵⁷ a metabolite of Stachyhotrys longispora³⁵⁸ has potential as a thrombolytic agent since it induces thrombolysis in a rat model of acute pulmonary thromboembolism without associated bleeding.³⁵⁹ Several studies have explored production of the lipopeptides scopularides A and B³⁶⁰ produced by Scopulariopsis brevicaulis (also known as Microascus brevicaulis). One study, the first proteome study of a marine fungus, determined that production levels of scopularides were not caused by changes in secondary metabolism, but by complex changes in primary metabolism.³⁶¹ Other studies^362,363 resulted in assembly of the genome of the fungus. Analysis of carbohydrate-active enzymes within a gene cluster led to the postulation that S. brevicaulis originated from a soil fungus which came in contact with the marine sponge Tethya aurantium.³⁶³

3.3 Fungi from mangroves

There has been a continued increase in the number of new metabolites reported from mangrove-associated fungi (127 in 2015 vs. 103 in 2014), with the majority coming from endophytic species. An Alternaria sp. yielded cylohexanone, cyclopentanone and xanthone derivatives 546–549 (ref. 364) and the genus Aspergillus was the source of many new metabolites including meroterpenoids 550–553,³⁶⁵ polyketides 554–556,³⁶⁶ indole diketopiperazines 557–559,³⁶⁷ isochromane derivatives 560–563 (ref. 368) and the versixanthones 564–567 and 568 and 569.³⁶⁹ The absolute configurations of these xanthone-chromanone dimers were established by a combination of techniques, including chemical conversions. A solvent-induced retro-oxa-Michael reaction was particularly helpful and indicated that 568 and 569 may in fact be artefacts of isolation. All of the versixanthones exhibited cytotoxicity at some level against several HTCLs and versixanthone E 568 was an inhibitor of topoisomerase I.³⁶⁹ Further metabolites obtained from the Aspergillus genus include dinapthalenone derivatives 570–573,³⁷⁰ lumazine peptide 574,³⁷¹ cyclohexanone-furan derivative 575, isocoumarin derivatives 576–578 and 579 (ref. 372) (first marine isolation)³⁷³ and polyene 580.³⁷⁴

New metabolites were obtained from the genera Botryosphaeria (isocoumarin 581 (ref. 375)), Cladosporium (dimeric tetralone 582 (ref. 376)), Daldinia (hydronaphthalenone 583 (ref. 377)), Eurotium (indolediketopiperazine 584 (ref. 378)), Eutypella (cytochalasans 585 and 586 (ref. 379) (new NP) and 587),³⁸⁰Fusarium (α-pyrones cladobotrin V 588 (ref. 381) and 589,³⁸² cyclic depsipeptides 590 and 591 (ref. 383)), Lophiostoma (phenalenone derivatives 592–600 and sesterterpene bipolarenic acid 601 (ref. 384)), Meyerozyma (depsidones 602–606 (ref. 385)), Nigrospora (acetamidopentane derivative 607 and phenalenone derivative 608 (ref. 386)) and Paradictyoarthrinium (hydroanthraquinones 609 and 610 (ref. 387)). The genus Penicillium was also the source of a number of new metabolites including polyketide decalins 611–616,³⁸⁸ sulfide diketopiperazines 617–621,³⁸⁹ pyrrole-4,5-dione derivative 622,³⁹⁰ polyketides 623–625 and 626 (ref. 391) (isolated for the first time as a NP) and compound 627,³⁹² citrinin analogues 628–630, xanthone derivative 631,³⁹³ compounds 632 and 633,³⁹⁴634 and 635,³⁹⁵ alkaloids 636 and 637,³⁹⁶ α-pyrones 638 and 639, dihydroxybenzoic acid derivatives 640 and 641, 642 and 643,³⁹⁷ (the last two are known compounds³⁹⁸) and polyketides 644–647.³⁹⁹ Pinazaphilone A reported in this paper³⁹⁹ is identical with pinophilin F 402 (ref. 258) reported in Section 3.2. An unusual benzodiazepine alkaloid 648 with a terminal cyano group was also obtained from a Penicillium sp. but was inactive towards a panel of HTCLs.⁴⁰⁰

Further metabolites were obtained from the genera Pestalotiopsis (prenylated phenols 649 and 650 (ref. 401)), Phomopsis (purine derivative 651 and octadecadiene derivative 652;⁴⁰² first isolation as a NP),⁴⁰³Setophoma (polyketides 653,⁴⁰⁴654 and 655, 656,⁴⁰⁵657 and 658, 659 (ref. 406)) and Stemphylium (aromatic sulfates 660 and 661 (ref. 407)). Stemphol⁴⁰⁸662 was obtained as a first time MNP.⁴⁰⁷ Several studies reported metabolites from species that were unidentified or only partially classified. Sesquiterpenoids 663 and 664 (ref. 409) and coumarin 665 (ref. 410) were obtained from unidentified species (the latter from a mixed culture of two species) and spirodioxynaphthalenes 666–670 (ref. 411) were obtained from a species of the order Pleosporales. Torrubiellin B⁴¹² was isolated for the first time as a MNP and the absolute configuration established as 671.⁴¹³ Synthesis of penicillenols B1 (ref. 414) and B2 (ref. 414) determined the stereochemistry of each as 672 and 673 respectively.⁴¹⁵ Synthesis of the proposed structures of cephalosporolides H⁴¹⁶ and I⁴¹⁶ has revised the configuration at C-6 of each to (R) (674 and 675) but discrepancies for some ¹³C NMR chemical shifts of the sidechain carbons between those reported for cephalosporolide I and the synthetic compound 675 indicate that the structure of cephalosporolide I may need further investigation.⁴¹⁷ Peniphenones A–D, polyketide metabolites of Penicillium dipodomyicola⁴¹⁸ have been synthesised via a biomimetic method⁴¹⁹ as has the Penicillium metabolite,⁴²⁰ (−)-penibruguieramine.⁴²¹Pestalotiopsis metabolite (6S,1′S,2′S)-hydroxypestalotin⁴²² has been synthesised⁴²³ and the proposed structure of pestalotioprolide A⁴²⁴ has been prepared via total synthesis, but a mismatch between the magnitudes of optical rotation data between the reported value for the natural product and the synthetic compound indicate that the stereochemistry of the natural product requires further examination.⁴²⁵ A number of known natural products were reisolated from Phakellia fusca and exhibited a range of activities. Penicillenol A₁,⁴¹⁴ a tetramic acid derivative, displayed anti-TB activity whilst expansols A–F^426,427 were potent COX-2 inhibitors and all but expansol D were also potent inhibitors of COX-1.⁴²⁸

3.4 Cyanobacteria

There has been an upturn in the number of new metabolites reported from cyanobacteria with 31 new metabolites reported in 2015 compared to 19 in 2014. Typical of the phylum, most of the metabolites reported were peptides. Linear lipopeptides 676 and 677 were obtained from Anabaena torulosa,⁴²⁹ from which the cyclic analogues laxophycins B^430–432 and B3 (ref. 431) had previously been obtained, posing the question as to whether the new compounds are enzymatic degradation products, isolation artefacts or true natural products.⁴²⁹ Further metabolites were obtained from the genera Hyalidium (new genus) (cyclic depsipeptides 678 and 679 (ref. 433)) and Lyngbya (lipopeptide 680 (ref. 434) and macrolides 681–683 (ref. 435)). A combination of mass spectrometric metabolic profiling and genomic analysis led to the isolation of the columbamides A–C 684–686 from Moorea bouillonii.⁴³⁶ These acyl amides 684–686 possessed moderate affinity for the CB₁ and CB₂ cannabinoid receptors. A similar approach was utilised in the isolation of hectoramide 687, hectochlorins B–D 688–690 and jamaicamides D–F 691–693 from M. producens.⁴³⁷ The terpene alkaloid 694 was also obtained from the genus Moorea.⁴³⁸

Bartolosides A–D 695–698 are chlorinated aromatic glycolipids obtained from a Nodosilinea species and Synechocystis salina respectively.⁴³⁹ Investigation of the biosynthesis of these molecules prior to completion of the structural assignment provided information that was vital to the structural elucidation of the chlorinated dialkylresorcinol core of these molecules.

Nodularia spumigena was the source of the pseudoaeruginosins NS1 699 and NS2 700, linear peptides which contain structural features of both the aeruginosins⁴⁴⁰ and the spumigens.⁴⁴¹ Structural characterisation of these metabolites was completed through synthesis and pseudoaeruginosin NS1 699 was a potent trypsin inhibitor.⁴⁴²

The genus Okeania was the source of the antimalarial polyhydroxy macrolide 701,⁴⁴³ the macrolactone 702 (ref. 444) and the lipopeptide kurahyne B 703.⁴⁴⁵ The related metabolite kurahyne A⁴⁴⁶ was also isolated and synthesised.⁴⁴⁵ An Okeania sp. was also the source of a new macrolide polycavernoside D 704.⁴⁴⁷ Polycavernosides^448–451 were previously implicated in fatal poisonings in the South Western Pacific and the source was ascribed to the red alga Polycavernosa tsudai. However, reisolation of these metabolites from the alga has never been achieved and they bear structural resemblance to known cyanobacterial metabolites. Furthermore, polycavernoside D 704 was obtained from a Caribbean cyanobacterial sample, implying that these toxins occur over a much wider geographical range than originally thought.⁴⁴⁷

A species that is most likely a new taxon but most closely related to specimens of the Hormoscilla genus yielded a tetrahydroquinolinol 705 (ref. 452) whilst a species only able to be identified as a member of the Oscilliatoriales family, was the source of the polyhydroxylated macrolides 706 and 707.⁴⁵³ Total synthesis of the cyclodepsipeptide coibamide A⁴⁵⁴ was achieved and resulted in the revision of the structure to 708 as a result of reassignment of two stereocentres.⁴⁵⁵ Two separate synthetic studies resulted in the structural revision of the lyngbyalosides. Total syntheses of the proposed⁴⁵⁶ and correct structures (709) of (−)-lyngbyaloside B were completed⁴⁵⁷ and total synthesis of the (18Z) and (18E) isomers of lyngbyaloside C⁴⁵⁸ resulted in reassignment of the structures to 710 and 711 respectively.⁴⁵⁹ As a result, it was suggested that the structure of lyngbouilloside⁴⁶⁰ should likely also be reconsidered.⁴⁵⁹ Total syntheses of the acyclic depsipeptide maedamide⁴⁶¹ and cyclodepsipeptide largamide B⁴⁶² also resulted in stereochemical revision of their structures to 712 (ref. 463) and 713 (ref. 464) respectively, the latter consistent with the revised structure previously proposed.⁴⁶⁵ Syntheses of (+)-lyngbyabellin M,^466,467 sanctolide A^468,469 and santacruzamate A^470,471 were also completed, with the last not exhibiting any inhibition of histone deacetylase (HDAC), unlike the potent inhibition previously reported.⁴⁷⁰ The functions of some enzymes involved in the biosynthesis of the terminal alkyne moiety in the jamaicamides⁴⁷² were elucidated via both in vitro and in vivo analyses.⁴⁷³ Dereplication methods based on phylogeny and HPLC-MS were developed which showed that largazole⁴⁷⁴ was always coproduced with either dolastatin 10 (ref. 475) or symplostatin 1 (ref. 476) and that combinations of largazole and dolastatin 10 displayed cooperative activity.⁴⁷⁷

3.5 Dinoflagellates

The number of new metabolites reported from dinoflagellates has remained the same as for 2014 with 15 compounds reported in each year. The genus Amphidinium has yielded new metabolites, including the linear polyketide 714,⁴⁷⁸ the macrolide 715,⁴⁷⁹ and the linear polyketide 716.⁴⁸⁰ Azaspiracids 717 and 718 were isolated from Azadinium poporum,⁴⁸¹ whilst the ladder polyether 719 was obtained from Gambierdiscus belizeanus.⁴⁸² Recent studies have shed some light on the biosynthetic pathway to paralytic shellfish toxins (PSTs) such as saxitoxin (STX).⁴⁸³ PSTs are known to be produced by both freshwater cyanobacteria and by dinoflagellates. Synthesis of some genetically predicted biosynthetic STX intermediates and identification of these in both a cyanobacterium and a dinoflagellate was previously reported.⁴⁸⁴ One of these intermediates has now been converted into cyclic-C′ 720, a tricyclic bisguanidine compound structurally related to STX. This metabolite was also identified in a PST-producing cyanobacterium and a dinoflagellate, suggesting that it is either a biosynthetic intermediate of STX or a shunt product of PSTs.⁴⁸⁵ Two karlotoxins 721 (ref. 486) and 722 (ref. 487) were obtained from a Karlodinium sp. as new MNPs and the stereochemistry of karlotoxin 2 (ref. 488) was revised to 723.⁴⁸⁹ The ciliate Spirostomum teres contains colourless extrusive organelles which function as a chemical defence.⁴⁹⁰ The tricyclic quinones spirostomin A 724 and B 725 were isolated from these organelles as a 5 : 1 diastereoisomeric mixture which was lethal to the ciliate Paramedcium caudatum at a relatively low dose. Total synthesis of each confirmed relative configurations.⁴⁹¹

Nonacosadienes 726 and 727 were obtained as metabolites of the microalga Emiliania huxleyi⁴⁹² while 12β-deoxydecarbamoylsaxitoxin⁴⁹³728 was obtained as a first time MNP.⁴⁹⁴ Syntheses of the polyketide amphirionin-4 (ref. 495) and ciguatoxin 54-deoxyCTX1B⁴⁹⁶ have been achieved.^497,498 Polyketide synthesis genes unique to two Gambierdiscus species that produce maitotoxin⁴⁹⁹ were characterised, perhaps implicating them in the biosynthesis of this metabolite.⁵⁰⁰ Studies with Karenia brevis showed that brevetoxin⁵⁰¹ is localised in the chloroplasts and interacts with light harvesting complex II (LHCII) and thioredoxin, so is likely implicated in non-photochemical quenching (NPQ). Differences between toxic and low toxicity K. brevis strains in NPQ and reactive oxygen species (ROS) production supported this.⁵⁰²

4 Green algae

The output of new compounds from the phylum Chlorophyta for 2015 was greater than that for recent years with eight new compounds noted from three publications. Noteworthy were the cyclic lipopeptides mebamamide A 729 and B 730 from Derbesia marina.⁵⁰³ This is a structural class rarely found in the Chlorophyta. Also reported were diterpenoids, 731–733, an α-tocopheroid 734, a sterol 735 along with 12 known compounds from Caulerpa racemosa⁵⁰⁴ and a triterpene acid 736 from Codium dwarkense.⁵⁰⁵ The diterpenoid 733 and the α-tocopheroid 734 are the first natural products to contain the haematinic acid and 3,5-dimethylphenoxy motifs respectively.

The structure and absolute configuration of nigricanoside A, isolated in 2007 from Avrainvillea nigricans,⁵⁰⁶ has been established by enantioselective total synthesis as 737, correcting aspects of the previously reported configurations.⁵⁰⁷ Originally isolated as the dimethyl ester, nigricanoside A was reported to inhibit the proliferation of several cancer cell lines (IC₅₀ 3 nM), but the synthetic material, identical in all respects to the natural sample, was inactive. The natural material was ∼90% pure and it is now suggested that the potent bioactivity of nigricanoside A was associated with a related, co-eluting minor metabolite with sub-nanomolar activity.⁵⁰⁷ An efficient and cost-effective method for the production of kahalalide congeners for advanced biological testing is based on the selective hydrolysis of N-protected kahalalide F isolated from nuisance blooms of Bryopsis pennata.⁵⁰⁸ By combining virtual- and structure-based ligand screening approaches, a database of >100 caulerpin analogues was efficiently evaluated in silico for potential inhibitory activity against monoamine oxidase B,⁵⁰⁹ while astaxanthin and other algal carotenoids have been the focus of many studies and reviews.^510–518

5 Brown algae

The level of interest in brown algae in 2015 was comparable to recent years with 33 new compounds reported from 12 papers out of a total of 54 papers and reviews on brown algae. Not atypically the chemistry was dominated by terpenoids and meroterpenoids with two dolastanes, 738 and 739, four xenicanes, 740–743 and two cytotoxic sterols 744 and 745 isolated from Canistrocarpus cervicornis,^519,520Dictyota plectens,⁵²¹ and Cystoseira trinodis⁵²² respectively. The compounds of mixed biosynthesis was a tranche comprised of a chromene, 746 (Homoeostrichus formosana),⁵²³ five acyclic meroditerpenoids 747–750, (Sargassum paradoxum)⁵²⁴751 (Cystophora retroflexa, C. subfarcinata, Sargassum cf. fallax),⁵²⁵ four cyclic meroditerpenoids 752 (Stypopodium flabelliforme),⁵²⁶753–755 (Stypopodium zonale)⁵²⁷ and the cyctophloketals A–E, 756–760, hybrid meroditerpenoids from Cystoseira tamariscifolia.⁵²⁸ The cyctophloketals, 756–760, each incorporated an O-methyltoluquinol and a phloroglucinol with the cyclic diterpene and are the first examples of meroterpenoids with the rarely found 2,7-dioxa-bicyclo[3.2.1]octane backbone.⁵²⁸ The proposed, unprecedented syn-cis-anti arrangement for the A/B/C ring system in the cyclic meroditerpenoid, O,C(3)-seco-9-ene-6β-taondiol 752 was based on NOESY data and supported the notion that the folding patterns of the presumed biosynthetic precursor, 2-geranylgeranyl-6-methylhydroquinone, are flexible during biosynthesis leading to different classes of metabolites related to the taondiol group.^528–531 The isolation and characterisation of >20 acyclic meroditerpenoids from a collection of seven Australian brown algae (and one red alga) included five new diterpenoids (747, 748, 749–751). This is an excellent example of the use of HPLC-NMR for the isolation and identification of unstable compounds (see 748 as a representative example).^524,525

The non-terpenoid brown algal compounds are represented by the polyketides, 761–770, from Lobophora variegata.⁵³² When considered as a group their biosynthetic origins can be rationalised by involvement of a non-acetate starter acyl-CoA, most likely a dodecanoic acid unit, and type III polyketide synthases.^533,534 The absolute configuration for the acylic diterpenoid elegandiol,^535,536771, was unequivocally re-established as (S) using VCD. This insightful paper outlines the approaches necessary for using VCD in the determination of absolute configuration.⁵³⁷ The first asymmetric synthesis of (−)-dolastatrienol (14-hydroxydolasta-1(15),7,9-triene)⁵³⁸ was reported⁵³⁹ along with a concise synthesis of dictyodendrins A and F.⁵⁴⁰ Additionally, there were many papers and reviews dealing with the biological properties of brown algal polyphenolics^541–557 and carotenoids.^15,558–562

6 Red algae

In 2015 twelve papers reported 33 new or revised structures from red algae. Of these papers, six described compounds from Laurencia spp. Twenty of the 33 compounds encompassed the typical structural types of fatty acid derivatives 772 and 773,⁵⁶³774,⁵⁶⁴775,⁵⁶⁵ oxosqualenoids 776–779,⁵⁶⁶ sesquiterpenoids 780 and 781,⁵⁶⁷782,⁵⁶⁸783,⁵⁶⁹784–785,⁵⁷⁰ diterpenoids 786–788,⁵⁷¹789,⁵⁷² and the mycosporine-like amino acid 790.⁵⁷³ The rearranged diterpenoids spirosphaerol 786 anthrasphaerol 787 and corfusphaeroxide 788 from Sphaerococcus coronopifolius have unprecedented tricyclic skeletons.⁵⁷¹

The remaining 13 compounds, the borolithochromes 791–803, were a series of polyketide-derived spiroborate pigments from samples of a more than 150-million-years-old Jurassic putative red alga Solenopora jurassica. The representative structures of borolithochromes G 791, H1 792 and H2 793 are shown here. The presence of boron in these structures as bis-six-membered spiroborates is unprecedented among present-day boron-containing natural products.

The rather unusual benzo[gh]tetraphene ligands have never been seen in any fossil compounds, and only recently a study⁵⁷⁴ of the anaerobic bacterium Clostridium beijerinckii revealed a polyketide antibiotic clostrubin A with similarities to the ligands in the borolithochromes. It was suggested that the fossil pigments may originally have been produced by an ancient bacterium, or have originated from bacteria that degraded the dead organic material of S. jurassica. In this remarkable piece of work, all structures were determined on samples of 6–57 μg, utilizing micro- and microcryo-probe NMR spectroscopy. Chiralities were established by comparison of experimental NMR shifts and CD spectra with results from DFT calculations.⁵⁷⁵ Syntheses of plocamenone and isoplocamenone have confirmed their structures⁵⁷⁶ and established their absolute configurations.⁵⁷⁷ Total syntheses of the proposed structures of microcladallenes A, B and C⁵⁷⁸ confirmed the structures of A and B but indicated that microcladallene C could not be correct.⁵⁷⁹ Additional studies on bis(2,3-dibromo-4,5-dihydroxyphenyl)-methane (Rhodomela larix)⁵⁸⁰ and bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (Odonthalia corymbifera)⁵⁸¹ have revealed significant activities in a range of assays, all indicating the potential of these compounds for development as anticancer agents.^582–584 Studies on eight brominated indoles from Laurencia brongniatii⁵⁸⁵ have revealed that some of them constitute a new class of relatively potent naturally occurring aryl hydrocarbon receptor (AhR) agonists.⁵⁸⁶

7 Sponges

The number of new sponge-derived metabolites described in 2015 (291) has remained relatively static when compared to previous years, with terpenoid compounds (130) being particularly dominant in number. A variety of ceramides 804–806,⁵⁸⁷ cerebrosides 807–815 (ref. 588) and 816–833,⁵⁸⁹ and lysosphingolipids 834 and 835 (ref. 590) were reported from Spheciospongia vagabunda, Aulosaccus sp. and Spirastrella purpurea, respectively, while the genera Biemna, Callyspongia, Haliclona and Xestospongia yielded taurinated 836,⁵⁹¹ polyunsaturated 837–839,⁵⁹²840 (ref. 593) and brominated 841 (ref. 594) fatty acids. Stelletta sp. provided six new glycosidated fatty acids stellettoside A1–B4 842–847. The structures of these N,N-dimethylputrescine-derivatives were established using a combination of advanced spectroscopic and degradative studies. The mixture of 842 and 843 was inactive against HeLa cells yet the mixture of 844–847 was cytotoxic (IC₅₀ 9 μM).⁵⁹⁵

Polyacetylenes were found in extracts of Callyspongia implexa848,⁵⁹⁶Petrosia sp. 849–851,⁵⁹⁷Halichondria sp. 852–854,⁵⁹⁷Pleroma sp. 855–861,⁵⁹⁸ and Xestospongia sp. 862 and 863.⁵⁹⁹ The nanomolar-scale isolation of mollenynes B–E 864–867 from Spirastrella mollis posed several challenges. First, the extremely low yields of isolated compound imposed limitations on acquiring usable NMR spectra, and second, unequivocal placement of the chlorine and bromine atoms upon the carbon backbone was difficult due to the similarity in ¹³C chemical shifts. The former issue was resolved by use of a cryogenically-cooled NMR microprobe while the latter exploited a new band-selective HSQC experiment for enhanced resolution by only detecting a small region of the ¹³C dimension. This facilitated the observation of the ³⁵Cl/³⁷Cl isotopic effect that causes a splitting of a chlorinated ¹³C resonance of around 1 Hz. The biosynthesis of these compounds could involve an unusual “dyotropic shift” of Cl and Br atoms, which would also account for the observed inversion of configurations within the series.⁶⁰⁰

The known fungal metabolites gibepyrones C 868 and F 869 (ref. 601) were isolated from the marine environment for the first time.⁶⁰² Sponges of the Plakortis genus are well known producers of methyl and ethyl branched polyketide peroxides. Studies of P. angulospiculatus870–872,⁶⁰³Plakortis sp. 873–875 (ref. 604) and P. bergquistae876–880 (ref. 605) were reported in 2015. Of note was the investigation of P. simplex which contained spiroplakortone 881. This modestly cytotoxic compound (IC₅₀ 37.5 μM against L5178Y mouse lymphoma) has an unprecedented spirocyclic core ring system and it suggested that it is formed via a hybrid polyketide/amino acid biosynthetic pathway. The structure of 881 was solved by a comprehensive combination of spectroscopic and computational studies to establish the configuration of the spiro-center.⁶⁰⁶

An unidentified sponge yielded two aromatic bases 882 and 883,⁶⁰⁷ while a mixture of Thorectid and Verongid sponges was the source of a new isoascorbic acid derivative 884, although this was speculated to be of fungal origin.⁶⁰⁸Euryspongia sp. from Okinawa yielded eurydiene 885 (ref. 609) while an Australian Dragmacidon sponge contained triphenyl 886.⁶¹⁰ Smenothiazoles A 887 and B 888 are two chlorinated thiazoles isolated from Smenospongia aurea (Little Inagua, Bahamas). These metabolites are of mixed PKS/NRPS origin that bears significant resemblance to the cyanobacterial compound jamaicamide B.⁴⁷² Both compounds showed in vitro inhibition of four solid HTCLs in the 1–100 nM range, and could selectively induce apoptosis in some cell lines via cell cycle blockage in the G_oG₁ phase.⁶¹¹

A surprisingly small number of peptides and depsipeptides were reported in 2015, given sponges are normally prolific reservoirs of such compounds. The α-ketoleucine or α-ketonorvaline-containing dimeric cyclopentapeptides nazumazoles A–C 889–891 (Theonella swinhoei) were detected as an exceedingly broad peak using ODS-HPLC and were isolated as an inseparable mixture. A significant number of degradative experiments were used to establish the dimeric structures, each joined through a single disulfide linkage. The mixture was cytotoxic to the P388 cell line (IC₅₀ 0.86 μM).⁶¹² Four collections of Callyspongia aerizusa from three different locations in Indonesia were sources of callyaerins I–M 892, 893, 894, 895 and 896. These new congeners were inactive against both M. tuberculosis and two HTCLs, even though related compounds were active in low μM concentrations, providing intriguing SAR. The reisolation of callyaerins D 897, F 898 and G 899,^613,614 previously isolated in vanishingly small quantities, allowed for complete structural elucidation which necessitated structural revisions as shown.⁶¹⁵

Stellettapeptins A 900 and B 901 are hybrid NRPS/PKS depsipeptides isolated from Stelletta sp. Structures were established using a combination of degradation studies and comprehensive NMR experiments. Both exhibited anti-HIV activity in HIV_RF-infected human T-lymphoblastoid cells with EC₅₀'s of 23 and 27 nM, respectively, with cytotoxicity vs. the parent cell lines only observed at 367 and 373 nM, giving a large degree of selectivity.^616,617 Macrolides were significantly reduced in numbers with just one report in 2015. Phormidolides B 902 and C 903 were isolated from a Petrosidae sponge (Pemba, Tanzania). Difficulties in assigning the relative configuration around the macrolide core necessitated the synthesis of three diastereomers of the lactone ring as a change in only one centre completely altered the NMR data for the entire ring system. Both compounds were cytotoxic to three HTCLs in the μM range.⁶¹⁸Hemimycale arabica and Acanthella cavernosa were sources of hemimycalins 904 and 905 (ref. 619) and diketopiperazines 906 and 907.⁶²⁰

Both enantiomers 908 and 909 of spirocyclic spiroreticulatine were isolated from Fascaplysinopsis. X-ray studies suggested the presence of a racemate, prompting the researchers to separate the compounds via chiral chromatography. The absolute configuration of each stereoisomer was determined by comparison of calculated and experimental ECD spectra. While both compounds inhibited IL-2 production at 15 μM, the dextrorotatory isomer was much more active than the levorotatory, while neither was cytotoxic at 50 μM vs. four HTCLs. A plausible biogenesis from tryptophan, glyoxal and dimethyl urea was proposed.⁶²¹

Three diamine-type alkaloids 910–912 were isolated from Indonesian Neopetrosia⁶²² and Acanthostrongylophora⁶²³ sponges, while a Neopetrosia sp. also yielded two nucleosides 913 and 914, one of which was also synthesised.⁶²⁴ Indole alkaloids were isolated from Ircinia915 and 916,⁶²⁵Plakortis917 and 918 (ref. 626) and Spongia919 and 920 (ref. 627) sponges. An Aaptos sponge yielded three aaptamine alkaloids 921–923.⁶²⁸ A Biemna sp. was the source of two pyridoacridines N-hydroxymethylisocystodamine 924 and neolabuanine 925. The structure assigned to 925 had previously been incorrectly attributed to labuanine A;⁶²⁹ the current study determined that this isolate was in fact ecionine A.⁶³⁰ Both compounds induced similar levels of cellular differentiation of human leukaemia tumour cells to normal erythrocytes at similar levels (ng mL⁻¹) to doxorubicin.⁶³¹

Guanidine-type alkaloids have been isolated from Biemna laboutei926–930,⁶³²Pseudoaxinella reticulata931–934,⁶³³Monanchora arbuscula935–940 (the synthesis of 935 was also achieved),⁶³⁴ and M. pulchra941–943,⁶³⁵ while oroidin-type pyrrolo-alkaloids were sourced from the genera Stylissa944 and 945 (ref. 636) and Agelas946 (synthesis also completed),⁶³⁷947 and 948,⁶³⁸949–951,⁶³⁹952–956.⁶⁴⁰ A series of bromotyrosine-derived compounds were reported from a member of the Verongida 957 and 958,⁶⁴¹Pseudoceratina arabica959–961,⁶⁴²P. purpurea962 and 963,⁶⁴³Acanthodendrilla sp. 964,⁶⁴⁴Suberea sp. 965–967 (ref. 645) and Aplysina lacunosa968–970.⁶⁴⁶ As always, prenylated metabolites dominate the compounds reported from sponges. Isolated meroterpenoids include 971–976,⁶⁴⁷977–984,⁶⁴⁸ and 985–987 (ref. 649) from Dysidea sponges. A novel approach was taken to promote the production of several “natural products”. Homogenised Verongula rigida, a sponge with known potent oxidative potential, was added to homogenised Smenospongia aurea and S. cerebriformis and incubated in ethanol for one week. LC-MS guided isolation of the Smenospongia extracts yielded several new 4,9-friedodrimane meroterpenoids 988–995. Whilst 992–995 are likely artefacts of the ethanol incubation, the other new compounds are all likely true biochemically-produced metabolites. The fused iminoquinone moiety of 990 and 991 is unprecedented in known natural products. Compounds 989–991 and 995 were moderately cytotoxic to two HTCLs.⁶⁵⁰ Puupehenol 996 (Dactylospongia sp.) exhibited pronounced anti-inflammatory activity. The known compound puupehenone⁶⁵¹ was also isolated. Exposing 996 to mild acid (CDCl₃) at slightly elevated temperatures (30 °C) resulted in quantitative conversion of puupehenol to puupehenone, suggesting the latter is actually an artefact of isolation.⁶⁵²

A series of adociaquinone compounds 997–1002 was reported from an Indonesian Xestospongia sp.,⁶⁵³ while meroditerpenoids 1003–1005,⁶⁵⁴1006,⁶⁵⁵1007 and 1008 (ref. 656) were isolated from Agelas nakamurai, Strongylophora strongylata, and Petrosia cortica respectively. Sesquiterpenoids 1009 and 1010,⁶⁵⁷ and 1011–1013 (ref. 658) were isolated from Dysidea fragilis and 1014–1018 from Halichondria sp.,⁶⁵⁹ while three farnesylacetone derivatives 1019–1021 were reported from Diacarnus megaspinorhabdosa.⁶⁶⁰Niphates and an unidentified Dictyoceratid sponge were the sources of 1022 (ref. 661) and 1023–1025,⁶⁶² respectively. Monamphilectines B 1026 and C 1027 are potent antimalarial β-lactams (IC₅₀ 44.5 and 43.3 nM vs. P. falciparum, respectively) isolated from Svenzea flava and were both synthesised from a known diisocyanide.⁶⁶³

Investigation of Hamigera tarangaensis revealed a series of brominated nitrogenous hamigeran diterpenoids 1028–1036. All incorporated an amino acid as part of the nitrogen heterocycle although stereochemical arguments required the inclusion of allo-isoleucine in 1035 and 1036 implying the intriguing possibility of a joint sponge/prokaryotic biogenesis.⁶⁶⁴ Sponges remain prolific producers of sesterterpenoids. Sarcotragin C 1037 was isolated from Sarcotragus sp.⁶⁶⁵ while a manoalide congener 1038 and several luffalides 1039–1044 came from Luffariella variabilis⁶⁶⁶ and Luffariella sp.,⁶⁶⁷ respectively. Two suvanine sesterterpenoid salts 1045 and 1046 were found from Coscinoderma sp.⁶⁶⁸ A large number of scalaranes 1047–1051,⁶⁶⁹1052 and 1053,⁶⁷⁰1054–1058,⁶⁷¹1059 and 1060,⁶⁷²1061–1071,⁶⁷³1072 and 1073 (ref. 674) were reported from five different sponge genera, Carteriospongia, Hyattella, Ircinia, Phyllospongia and Spongia respectively. Other new sesterterpenoids were 1074 and 1075 (Clathria gombawuiensis)⁶⁷⁵ and 1076 (Haliclona sp.) sourced from Korean collections.⁶⁷⁶

Several new sterols and their degradation products have also been reported from sponges. Epoxide- 1077 and peroxide-1078–1079 containing sterols were found from Biemna⁵⁹³ and Monanchora⁶⁷⁷ sponges, respectively, while highly derivatized sterols were isolated from Dragmacidon australe1081 (ref. 610) and Polymastia boletiformis1082 and 1083.⁶⁷⁸ A new 9,11-secosterol 1084 came from a Korean Ircinia sp.⁶⁷⁹ The first naturally occurring bicyclo[4,3,1]-A/B ring system steroids, monanchosterol A 1085 and B 1086, were isolated along with a third sterol 1087 from Monanchora sp. (Gageo Is., Korea). The biogenesis of the ring-contracted compounds was suggested to begin from a common 4β,5β-epoxysterol. The only other report of such a ring system is from a synthetic study published by Barton in the 1980s.⁶⁸⁰ While 1085 was toxic to RAW264.7 cells (IC₅₀ 65 μM), both 1086 and 1087 were not, but instead were immunomodulatory inhibiting mRNA expression of IL-6 by ∼70% at 10 μM even though monanchosterols A and B only differ by a single acetylation.⁶⁸¹

A nortriterpenoid-saponin 1088,⁶⁷⁵ and nine other triterpenoids 1089–1096 (ref. 682) and 1097 (ref. 683) were reported in 2015. Additionally, the new compounds stellettins N–P 1098–1100 were isolated from Stelletta tenuis⁶⁰² although the name stellettin N had been used previously for a different structure.⁶⁸⁴ The absolute configuration of psammaplysin A 1101 (ref. 685) (isolated in the current study from Aplysinella strongylata) was established from detailed comparison of calculated and experimental ECD data in conjunction with NMR studies including Mosher's analysis,⁶⁸⁶ while the absolute configuration of euryspongin A 1102 (Euryspongia sp.) was also determined using chiroptical techniques.⁶⁰⁹ Inconsistencies in NMR data reported for two sponge sterols isolated from Neofibularia nolitangere⁶⁸⁷ with those isolated from Japanese edible mushrooms necessitated structural revision to 1103 and 1104.⁶⁸⁸ Hepatitis B infection poses a major human health risk. Two sponge-derived polybrominated biphenyls^689,690 isolated from Indonesian Dysidea species were found to possess hepatitis antiviral activity with selectivity indices of 12.8–18.2.⁶⁹¹ Transcriptomic analysis of HepG2 hepatocarcinoma cells treated with both Crambe crambe metabolites crambescin C1 (ref. 692) and A1 (ref. 693) showed that the former protects against cytotoxic oxidative damage by induction of metallothionein, while the latter is ineffective.⁶⁹⁴ The bastadin-class of bromotyrosine compounds, in particular bastadin-6,⁶⁹⁵ suppress foam formation in macrophages via inhibition of cholesterol-ester formation, and may have application in the treatment of artherosclerosis.⁶⁹⁶ Panicein A hydroquinone⁶⁹⁷ (Haliclona mucosa) inhibits the efflux of doxorubicin by the Hedgehog receptor Patched and enhances the anticancer efficacy of the drug.⁶⁹⁸ A hypothesis put forward over a decade ago that marine isonitriles and isothiocyanates may exert the antiplasmodial activity via interference of heme detoxification⁶⁹⁹ has been corroborated. The mode of action of these compounds was assessed using a scaled-down version of Egan's β-hematin assay demonstrating that marine isonitriles inhibit β-hematin crystallisation and supported by ab initio calculations of the stability of the isonitrile complexes bound to iron in heme.⁷⁰⁰ Gracilins A, H and L^701,702 along with tetrahydroaplysulphurin-1,⁷⁰³ all isolated from Spongionella sp., were found to modulate mitochondrial function in neuroblastoma cells by regulating storage of calcium entry in a similar manner to cyclosporine A via binding to cyclophilin D.⁷⁰⁴ Okadaic acid (OA), a potent marine cytotoxin that inhibits protein phosphatases, was originally isolated from Halichondria okadai but later identified as being produced by the dinoflagellate Prorocentrum lima and actively bioaccumulated by the sponge.⁷⁰⁵ The role and mechanism of OA accumulation by Halichondria has not yet been established. Exposure of an extract of H. okadai to OA indicated strong binding to two proteins, OA Binding Proteins (OABP) 1 and 2. While unsurprisingly OABP1 is a protein phosphatase, OABP2 is not. The X-ray crystal structure of OABP2.1 obtained from H. Okadai bound to OA showed that it has significant binding affinity for OA and has a limited homology to known protein scaffolds. Surprisingly, the global fold of OABP2.1 was most similar to the jellyfish Ca²⁺-binding photoprotein aequorin. Ca²⁺ does not displace OA from its binding site, suggesting a different mechanism for OA release by the sponge.⁷⁰⁶ A comprehensive LCMS analysis of 253 Aplysina sponges comprising ten different morphologies showed that the sponge secondary metabolome correlates better with the sponge phenotype, described by invertebrate morphology, rather than the microbiome.⁷⁰⁷ The ability of 26 sponges to inhibit bacterial quorum-sensing without cytotoxic activity was investigated. The extract of Ircinia felix was found to be the most potent inhibitor of quorum-sensing with the activity linked to the felixinin furanosesquiterpenoid class.^708–710 Chemical examination of adult and bud larvae of the chemically-defended sponge Tethya maza indicated that the sterol composition of both were largely similar, suggesting that the larvae are also defended during reproduction.⁷¹¹ First total syntheses were reported for many compounds including the lipids motualevic acid F, (E)- and (Z)-antazirine,^712–714 mycalol (revised to 1105)^715–717 and myrmekioside A,^718,719 and polyacetylenes callyspongynic acid,^720,721 phosphoiodyn A and placotylene A.^722–725 The structure of plakinidone has been corrected to 1106; the compound is highly sensitive to air oxidation. The compound's relative configuration was also determined,^726,727 while the relative configuration of the C-36 to C-42 portion of hemicalide 1107 was also solved by synthesis.^728,729 Total syntheses of polyketides gracilioether B and C^730,731 and hippolachnin,^732,733 mycothiazole,^734–736 aromatic renieramycin I,^737,738 and peptides cyclocinamide A,⁷³⁹ corticiamide B,^740–742 stylissamide X^743,744 and stylissatin A^745,746 have all been realised. The total synthesis of yaku'amide A 1108, including eight possible stereoisomers of its core region, required revision of structure, and also that of congener B 1109.^747,748 Macrolides are attractive targets for synthesis with the construction of tulearin A,^749,750 mycalolide B,^751,752 and muironolide A 1110 being completed, the latter requiring a structural revision.^753,754 Pyridines nakinadine D–F,^755,756 indoles scalaridine A,^757,758 dragmacidin D 1111,^759–761 dendridine A,^762,763 and guanidine batzelladine B^764,765 are alkaloid compounds that have all been synthesised. Although the stereoselective synthesis of palau'amine has been achieved before,⁷⁶⁶ the construction of the ABDE tetracyclic core in one cascade step is a very significant improvement in the production of this important marine metabolite.⁷⁶⁷ Clavatadine A,^768,769 aplysinellamides A and B,^770,771 and 11-deoxyfistularin-3 (ref. 772 and 773) were synthesised for the first time. Meroterpenoids that had initial total syntheses are panicein A₂,^774,775 dictyoceratins A⁷⁷⁶ and C,^777–779 and neopetrosiquinones A and B.^780,781 The structure of siphondictyal B⁷⁸² has been revised to 1112, based upon total synthesis. The biomimetic conversion of siphondictyal B to liphagal⁷⁸³via a stable o-quinone methide supports a novel biogenetic proposal.⁷⁸⁴ The sesquiterpenoids aignopsanoic acid A, methyl aignopsanoate and isoaignopsanoic acid A⁷⁸⁵ have been synthesised, with absolute configurations and that of the related compound microcionin-1 1113 (ref. 786) established.⁷⁸⁷ Several diterpenoids have succumbed to total synthesis: viz. spongiolactone^788,789 debromohamigeran E,^790,791 and kalihinol B.^792,793 While the racemic synthesis of ambliol A had earlier been achieved,^794,795 the first enantioselective synthesis has established the absolute configuration as 1114.⁷⁹⁶ The total syntheses of the sesterterpenoids phorbin A,^797,798 luffarins L and I,^799–801 salmahyrtisol A⁸⁰² and hippospongide A^803,804 have been finalised.

8 Cnidarians

The low number of new compounds reported from cnidarians in 2015 (143) is 40% below the previous decadal average. The chemistry of cnidarians is typically dominated by compounds of terpenoid origin. In 2015 there were a limited number of alkaloids isolated from both soft and hard corals, including the anxiolytic ceramide 1115 (Sarcophyton auritum),⁸⁰⁵ the diaminopropyl analogue 1116 (Paraplexaura sp.),⁸⁰⁶ and new examples of zoanthenamines 1117–1123 from the hard coral Zoanthus kuroshio.⁸⁰⁷ The simple cinnamate ester 1124 was isolated from Sarcophyton ehrenbergi and the structure confirmed and absolute configuration assigned by stereoselective synthesis.⁸⁰⁸ A series of seventeen sesquiterpenes were reported, comprised of a himachalene-type peroxide 1125 (Litophyton arboretum),⁸⁰⁹ cyclopentenones 1126 (Sinularia sandensis)⁸¹⁰ and 1127 and 1128 (Sinularia acuta),⁸¹¹ eudesmane-type 1129 (Sinularia gaweli),⁸¹² subergane-type 1130 (Subergorgia suberosa),⁸¹³ monocyclic and bicyclic germacrenes 1131 (Sarcophyton glaucum)⁸¹⁴ and 1132 and 1133 (Capnella sp.),⁸¹⁵ caryophyllanes 1134 and 1135 (Rumphella antipathies),⁸¹⁶ and guaiane lactones 1136–1140 (Menella kanisa)⁸¹⁷ and 1141 and 1142 (Menella woodin).⁸¹⁸ Of note was the use of a diverse array of computational techniques, including calculated ¹³C NMR chemical shifts, optical rotation and ECD to determine the structures and absolute configurations of 1141 and 1142.

Of four tocopherol-derived metabolites 1143 and 1144 (ref. 819) and 1145 and 1146,⁸²⁰ hirsutocospiro A 1143 exhibited strong anti-inflammatory activity and cladophenol glycosides A 1145 and B 1146 exhibited mild cytotoxicity towards three HTCLs. Thirty-one cembrane-related metabolites reported from cnidarians in 2015 included 1147 (Sarcophyton glaucum),⁸¹⁴ epoxynephthenols 1148–1150 (field-collected Nephthea columnaris),⁸²¹ columnariols A 1151 and B 1152 (cultured N. columnaris),⁸²² sarcophine and ehrenbergol congeners 1153–1157 (Sarcophyton ehrenbergi),⁸²³cis-cyclopropylated casbanes sinularcasbane G–L 1158–1163 (Sinularia sp.),⁸²⁴ sarcophelegans A–D 1164–1167 (Sarcophyton elegans),⁸²⁵ tricyclic 1168 (Sarcophyton solidum),⁸²⁶ pyrans 1169 and 1170 (Sarcophyton trocheliophorum)⁸²⁷ and 1171 (Litophyton arboreum),⁸⁰⁹ hydroperoxycembranoid 1172 (Sarcophyton trocheliophorum),⁸²⁸ and 1173–1177 (Sinularia sandensis and S. flexibilis).⁸²⁹ X-ray studies were used to determine the complete structural and stereochemical characterization of sarcophelegan A 1164,⁸²⁵ cembranoid 1173 and isosinulaflexiolide K 1177.⁸²⁹ X-ray studies were also used to confirm the structures and configuration of previously reported cembranoids sarsolilide B (Sarcophyton trocheliophorum)^826,830 pukalide (Leptogorgia alba)⁸³¹ and dendronpholide F (Dendronephthya sp.)^829,832 The trivial name epoxynephthenol assigned to 1150 (ref. 821) has been used previously.⁸³³

A series of nitrogenous diterpenoids and sesquiterpenoids 1178–1187 were reported from Cespitularia taeniata – the absolute configuration of cespilamide A 1178 was established by a combination of MM2 modeling and Mosher's analysis.⁸³⁴ Rare examples of cembranoid 7,8-diols 1188 and 1189 were isolated from Sinularia gaweli.⁸¹² The structure assigned 1188 is the (−)-enantiomer of the known cembranoid leptodiol acetate (Leptogorgia sp.),⁸³⁵ while 1189 was found to be a potent inhibitor of pro-inflammatory iNOS production in LPS-stimulated murine macrophages.

Norcembranoids 1190 and 1191 (Sinularia numerosa)⁸³⁶ were unfortunately given the trivial names sinumerolide A and (7E)-sinumerolide A, names previously attributed to cembranoids reported from the same organism.⁸³⁷ From a structural point of view, the metabolites are simply methyl ether variants of the previously reported ethyl ether leptocladolide A and its (7E) isomer.⁸³⁸ A mildly cytotoxic norcembranoid 1192 was isolated from cultured specimens of S. numerosa.⁸³⁹ Six α-methylene-γ-lactone cembranoids 1193–1198, epoxide 1199 and bis-cembranoid sinulaflexiolide L 1200 were reported from Sinularia flexibilis.⁸⁴⁰ The structure and relative configuration of 1200 and absolute configuration of known co-metabolite sinuflexolide⁸⁴¹ were secured by X-ray studies.

Cytotoxic and anti-inflammatory bis-cembranoids glaucumolide A 1201 and B 1202 were isolated from cultured specimens of Sarcophyton glaucum,⁸⁴² while of sarcophytolides M 1203 and N 1204, only the former exhibited cytotoxicity to a panel of HTCLs.⁸⁴³ Eight new briarane-skeletoned diterpenes were reported in 2015 (briarenolides K 1205, L 1206 (ref. 844) and U–Y 1207–1211,⁸⁴⁵Briareum sp.; dichotellide V 1212,⁸⁴⁶Dichotella gemmacea). All the briarenolides were found to inhibit production of the pro-inflammatory inducible nitric oxide synthase (iNOS), while briarenolides U–Y also inhibited the product of COX-2 in LPS-stimulated macrophage cells. Of the remaining nine diterpenes, three were xenicanes (1213–1215, unnamed, Xenia sp.),⁸⁴⁷ and six were eunicellins (1216 and 1217,⁸⁴⁸Muricella sibogae; 1218–1221,⁸⁴⁹Cladiella hirsuta). Of note was that the structure of 1213 was secured by X-ray studies.

From the cnidarians a variety of steroids were isolated that included pregnane glycosides (1222 and 1223, Cladiella hirsuta),⁸²⁰seco-sterols (1224–1229, Subergorgia suberosa)⁸⁵⁰ a seco-ketosterol hydroperoxide 1230 (Litophyton arboretum),⁸⁰⁹ ketosterols (1231–1233, Subergorgia rubra),⁸⁵¹ hydroxylated/polyhydroxylated sterols (1234–1237, Sinularia acuta;⁸¹¹1238–1243, Palythoa tuberculosa;⁸⁵²1244–1249 and known 1250, Klyxum flaccidum;⁸⁵³1251–1254, Menella woodin;⁸⁵⁴1255, Dichotella gemmacea⁸⁵⁵) and a steroidal glycoside (1256, Sinularia nanolobata).⁸²⁰ The C-24 configuration of 1250 was corrected by comparison with related MNPs. Investigation of MNP chemistry of sea anemones has identified two new imidazolones 1257 and 1258 from the sea anemone Heteractis aurora.⁸⁵⁶ Absolute configurations were assigned by stereoselective synthesis of the corresponding enantiomers, with the magnitudes of optical rotation observed indicating the natural products had been isolated as scalemic (partially racemic) mixtures. Further studies of toxins from anemones has revealed two new examples of HCRG polypeptides (>6 kDa) from Heteractis crispa,⁸⁵⁷ the toxicity of the α-pore-forming toxin equinatoxin II depends upon its ability to assemble into oligomers on the cell surface,⁸⁵⁸ while N-terminus modified analogues of the 35-residue disulfide-rich toxin ShK from Stichodactyla helianthus showed enhanced selectivity towards voltage-gated potassium channel Kv1.3 versus other subtypes, making them of clinical interest for the treatment of autoimmune diseases.^859,860 A comprehensive sequence alignment study of cnidarian toxins suggests a common origin of sodium channel and a subtype of potassium channel toxins in sea anemones and that pore-forming toxins have evolved under strong evolutionary constraints.⁸⁶¹

As noted in last year's review,¹ clarification of the structures of cladiellin diterpenes including the sclerophytins (Sclerophytum capitalis)⁸⁶² is an ongoing issue. Based upon re-analysis of NMR data Friedrich and Paquette in 2002 proposed a number of structural revisions.⁸⁶³ Synthesis of the purported structure of sclerophytin F as well as three diastereomers, combined with re-examination of published NMR data, has led to the conclusion that sclerophytins E and F are in fact the same compound 1259.⁸⁶⁴ The study concluded that all sclerophytins share the sclerophytin A skeleton with variation of acylation at the C-3 and C-6 positions and that the C-3 configuration inversions proposed by Friedrich and Paquette are incorrect. The structure of litophynin E (Litophyton sp.)⁸⁶⁵ should be corrected to the C-7 epimer 1260. The structures and absolute configurations of (+)-uprolide F diacetate 1261 and (+)-uprolide G acetate 1262 (Eunicea mammosa)⁸⁶⁶ have been revised (again)⁸⁶⁷ and confirmed by total synthesis.^868,869

A stereodivergent synthesis of four diastereomers has established the structure and absolute configuration of solandelactone I (Solanderia secunda)⁸⁷⁰ to be 1263,⁸⁷¹ while total synthesis of the enantiomer has led to correction of absolute configuration of (−)-suberosanone (Isis hippuris)⁸⁷² to 1264.⁸⁷³ The structures of clavulolactones II and III⁸⁷⁴ (Clavularia viridis),⁸⁷⁵ tubastrine⁸⁷⁶ (Tubastrea aurea⁸⁷⁷ as well as ascidians^878,879) and breitfussin A and B^880,881 (Thuiaria breitfussi)⁸⁸² have been confirmed by total synthesis.

Further biological studies of lipids and sterols from Eunicea fusca and Eunicea sp. have identified some to exhibit anti-biofilm action in the absence of antimicrobial effects,⁸⁸³ alcyonolide-type diterpenes (Cespitularia sp.) exhibit cytotoxicity towards HCT-116 cells via induction of caspase 3/7 activity and suppress pro-inflammatory iNOS and COX-2 gene expression,⁸⁸⁴ cembranoids exhibit peroxisome proliferator-activated receptor transactivational effects,⁸⁸⁵ antiprotozoal activities,⁸⁸⁶ antiosteoporotic and antioxidant activities,⁸⁸⁷ hepatocellular carcinoma cell migration and invasion,⁸⁸⁸ and antiproliferative activity through activation of the transforming growth factor-beta (TGF-β) pathway.⁸⁸⁹ Excavatolide B, a briarane diterpenoid originally isolated from Briareum excavatum, exhibits anti-inflammatory and analgesic effects in vitro and in in vivo models.⁸⁹⁰ Two sesquiterpenes, (Z,E) and (E,E)-germacrones, constituents of the gorgonian Phyllogorgia dilatata, are odiferous volatiles with fragrant, marine and slightly woody odours with citrus aspects.⁸⁹¹ Finally, amphidinolide P, originally reported from the marine dinoflagellate Amphidinium sp., was isolated from the octocoral Stragulum bicolor and also in its predator, the nudibranch Marionia limceana.⁸⁹² A likely artifactual methyl acetal derivative of amphidinolide P was also isolated from the octocoral.

9 Bryozoans

There were five reports (containing 9 compounds) of new metabolites isolated from bryozoans in 2015 compared to three reports (containing 18 compounds) in 2014, so interest in this understudied phylum continues to increase very slowly. The tribrominated alkaloid kororamide B 1265 was isolated from Amathia tortuosa, along with kororamide A⁸⁹³ and convolutamines I⁸⁹⁴ and J.⁸⁹⁴ All four compounds induced a phenotypic signature in a cell line derived from a Parkinson's disease patient indicative of effects on vesicular trafficking, a process recently implicated in the disease.⁸⁹⁵ The tripeptide janolusimide B 1266 is the first peptide to be isolated from a bryozoan and was obtained from Bugulina flabellata.⁸⁹⁶ Janolusimide B is an N-methyl analogue of janolusimide,⁸⁹⁷ which was isolated from a Mediterranean nudibranch, Janolus cristatus, a known predator of bryozoans. Hydrolysis, derivatisation and stereoselective synthesis of fragments were utilised to establish the stereochemistry.⁸⁹⁶ Four new bryostatins,⁸⁹⁸ bryostatin 21 1267, and 9-O-methylbryostatins 4, 16 and 17 1268–1270 were obtained from Bugula neritina although it is probable that 1268–1270 are artefacts since the solvent used for extraction was methanol.⁸⁹⁹ The known synthetic compound p-methylsulfonylmethyl-phenol^900,9011271 was obtained as a first time NP and monoheneicosanoin⁹⁰²1272 was obtained as a new MNP from Cryptosula pallasiana.⁹⁰³ Synthesis of amathamide F originally obtained from Amathia wilsoni⁹⁰⁴ has confirmed the revision of the structure proposed in 2011 (ref. 905) (1273).⁹⁰⁶

10 Molluscs

The number of new metabolites reported from molluscs (43) is a substantial increase in the average number reported per year over the past decade. Azaspiracids 7–10 1274–1277 were isolated from extracts of the mussel Mytilus edulis and the structures characterised by NMR and mass spectrometry.⁹⁰⁷ Azaspiracid 8 was approximately an order of magnitude more cytotoxic towards Jurkat T lymphocytes than either of azaspiracids 9 and 10. The neurotoxic effects of azaspiracid 1 have been investigated using PC12 cells, whereby exposure induced early differentiation and down-regulation of the neurospecific intermediate filament protein peripherin.⁹⁰⁸ Crystal structures of pinnatoxins A and G bound to acetylcholine-binding protein, a surrogate for their cellular nAChR target, have identified the attributes required for tight binding and receptor subtype selectivity.⁹⁰⁹ Electrophysiological and competiton binding experiments have identified that 13-desmethyl spirolide C is a potent but relatively non-selective ligand of nAChRs while 13,19-didesmethyl spirolide C is more selective of the muscular-type receptor.⁹¹⁰ Both MNPs interacted weakly with muscarinic AChRs. Further investigation of the unusual occurrence of tetrodotoxin in New Zealand collections of the nudibranch Pleurobranchaea maculata has led to the metabolite being detected in mucin cells, the mantle, gonad tissue and the digestive gland of the nudibranch as well as in the larvae and eggs but not in the gelatinous egg cases.⁹¹¹ These findings suggest the toxin is of dietary source and may play a defensive role in the nudibranch. Nudibranchs were the sources of a homosesterterpene 1278 (Charcotia granulosa),⁹¹² a series of antimalarial isocyano and isothiocyanato sesquiterpenes 1279–1283 (Phyllidia ocellata),⁹¹³ scalarane sesterpenes 1284 and 1285 (Glossodoris hikuerensis) and diterpene 1286 (Goniobranchus albonares),⁹¹⁴ norscalaranes 1287–1296 and spongian diterpenes 1297–1305 (Dorisprismatica (= Glossodoris) atromarginata).⁹¹⁵ Granuloside 1278 is the first example of a linear homosesterterpene.⁹¹² Absolute configuration was assigned by comparison of experimental and calculated ECD data. The structure and absolute configuration of 2-isocyanoclovene 1279 was secured by X-ray crystallographic analysis of a formamide derivative.⁹¹³

Two studies of sea hares identified eight new dactylomelane diterpenes 1306–1313 from a Greek collection of Aplysia depilans,⁹¹⁶ while a Japanese collection of A. kurodai was the source of modestly cytotoxic 9,11-secosteroid aplysiasecosterol A 1314.⁹¹⁷ The absolute configuration of 1314 was established by comparison of calculated and experimental ECD data using a simplified model of the tricyclic γ-diketone core of the MNP and by modified Mosher's analysis.

Re-examination of extracts of Elysia crispata (Venezuela) has led to the characterisation of (−)-phototridachiahydropyrone 1315,⁹¹⁸ a molecule previously speculated to be a MNP based upon its biomimetic photochemical formation from the related metabolite tridachiahydropyrone.⁹¹⁹ Surface-assisted mass spectrometry, whereby on-surface solvent extraction of small molecules onto nanostructured or porous silicon surfaces, has been used to image the distribution of choline esters, brominated indoles and lipids in the tissue of the mollusc Dicanthais orbita.⁹²⁰ 6-Bromohypaphorine (Hermissenda crassicornis), previously known as a sponge^921,922 and tunicate metabolite,⁹²³ is a mild agonist of human α7 nAChR but shows no effect on muscle-type nAChR from Torpedo californica.⁹²⁴ Dolastatin 16 obtained by total synthesis⁹²⁵ was found to be inactive, in contrast to the potent cytotoxicity towards HTCLs originally attributed to the MNP (Dolabella auricularia).⁹²⁶ New examples of M- and T-superfamily peptides were isolated from Indian collections of Conus araneosus⁹²⁷ and C. figulinus⁹²⁸ while analysis of venom duct cDNA from C. litteratus⁹²⁹ and C. marmoreus⁹³⁰ prompted the cloned expression or chemical synthesis and subsequent biological evaluation of new peptides. Highly detailed transcriptome analysis of C. episcopatus identified over 3300 novel full-length conotoxin precursors which represented 9 known and 16 new gene superfamilies.⁹³¹ Six novel cysteine frameworks were identified, providing impetus for further toxin discovery in Conus snails. Two studies in particular reported metabolites that expand the chemical repertoire of Conus molluscs. In the first of these, a simple guanine derivative, genuanine 1316 was isolated from C. genuanus and the structure confirmed by synthesis.⁹³² Compound 1316 exhibited potent paralytic activity in mice, mimicking the activity of the crude venom extract.

A small library of analogues representing desmethyl and/or propionate sidechain positional isomers were all devoid of activity. At the other molecular weight extreme, a specialised insulin Con-Ins G1, bearing post-translational modifications characteristic of conotoxins, e.g. hydroxyproline and γ-carboxyglutamate, was isolated from the venom of the fish-hunting C. geographus.⁹³³ The protein, which has greater sequence similarity to fish insulins than to mollusc versions, elicits hypoglycemic shock in fish, facilitating prey capture by the snails distended false mouth, the so-called ‘net strategy’. Further variants were discovered upon closer examination of the venom extract by MS. A selenocysteine analogue of Con-Ins G1 was synthesised and was found to induce similar effects including being active when added to the water column. Fish-like insulin sequences were also identified in another fish-hunting species, C. tulipa, that also uses the net strategy, whereas sequences were absent in harpoon-method fish hunters.⁹³³

11 Tunicates (ascidians)

The eighteen new tunicate-derived natural products presented in this review is the second lowest annual count since 2002. The metabolites reported included a meroterpenoid 1317,⁹³⁴ an array of halogenated alkaloids 1318–1323 (ref. 935) and 1324,⁹³⁶ taurine amides 1325–1327,⁹³⁷ purines 1328–1331,⁹³⁸ a new pyridoacridine 1332 (ref. 939) and two unusual tetracyclic-cored alkaloids 1333 and 1334.⁹⁴⁰ Noteworthy were the isolation, structure elucidation, synthesis and biological evaluation of eudistidines A 1333 and B 1334 (Eudistoma sp., Palau).⁹⁴⁰ A four-step condensation/cyclisation reaction sequence afforded both natural products, allowing confirmation of their structures. Eudistidine A was found to inhibit an essential protein–protein interaction (p300-HIF-1α) required for HIF-1α (hypoxia-inducible factor 1) activation: such inhibitors could find therapeutic use as antitumour agents by acting to down-regulate the expression of hypoxia-selective genes.

An expeditious total synthesis of shishijimicin A⁹⁴¹ has been reported,⁹⁴² confirming the structure and opening the door for further biological evaluation of this potently cytotoxic enediyne. The structure of tunichrome Sp-1 (ref. 943) has been confirmed by total synthesis⁹⁴⁴ and a new catalytic asymmetric synthetic route to (−)-perophoramidine⁹⁴⁵ has been disclosed.⁹⁴⁶ Cell-cycle arrest at the G₂/M phase and induction of apoptosis in HeLa cells⁹⁴⁷ was observed for the ascidian alkaloid eudistomin H,⁹⁴⁸ while eusynstyelamide B⁹⁴⁹ also induces G₂/M phase arrest, causes double strand breaks in DNA and is a topisomerase II poison.⁹⁵⁰ Further investigation of clavanin A, a C-terminal amidated 23 residue antimicrobial peptide,⁹⁵¹ has identified it to exhibit no cytotoxicity and to be active in vivo and in a wound healing model of S. aureus infection.⁹⁵² Preliminary investigation of anti-angiogenic activity in myxoid liposarcomas has identified trabectedin (Yondelis^®, Et-743) as an upregulator of inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2, and of TSP-1, a key regulator of angiogenesis-dependent dormancy.⁹⁵³ For several decades, didemnin B and related analogues have been the subject of numerous clinical trials, ultimately resulting in dehydrodidemnin B (Aplidine) being granted orphan drug status towards acute lymphoblastic leukemia. Gene-expression mapping has identified didemnin B to be a dual inhibitor of palmitoyl-protein thioesterase (PPT1) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), the combination of which leads to apoptosis and antineoplastic activity.⁹⁵⁴ Gene expression data from cancer cell lines that were either sensitive or resistant to didemnin B identified four gene biomarkers that correlated with sensitivity to the natural product. These biomarkers, associated with epithelial-derived cell lines and also some colorectal, breast and lung cell lines, could be of use in predicting the likelihood of patient response to didemnin B or analogues in a therapeutic setting. Synthetic analogues related to the polyandrocarpamines⁹⁵⁵ were found to be inhibitors of H₂S production by cystathionine beta-synthase,⁹⁵⁶ and SAR studies have been reported for thiaplidiaquinones A and B⁹⁵⁷ (various biological targets),⁹⁵⁸ cadiolides A–C^959,960 (antibacterial),^961,962 rubrolides⁹⁶³ (photosynthesis inhibitors),⁹⁶⁴ meridianins⁹⁶⁵ (antimalarial and antituberculosis),⁹⁶⁶ isogranulatimide⁹⁶⁷ (cytotoxicity),⁹⁶⁸ and lamellarins⁹⁶⁹ (cytotoxicity).⁹⁷⁰

12 Echinoderms

The twenty-seven new metabolites reported from echinoderms in this review is just over half the average number reported per annum over the last decade. A new carotenoid 1335 was reported from Plesiocolochirus minutus, with absolute configuration assigned by a combination of ECD and NOESY analysis,⁹⁷¹ while the structure of 3′-epigobiusxanthin (Crown-of-thorns Acanthaster planci)⁹⁷² has been corrected to that of 6′-epigobiusxanthin 1336 as a consequence of stereospecific synthesis of a series of stereoisomers.⁹⁷³ The remaining metabolites reported from echinoderms were of saccharide or sterol/sterol glycoside origins and included 1337 (starfish Asterias rollestoni)⁹⁷⁴1338–1341 (starfish Leptasterias ochotensis),⁹⁷⁵1342 (sea cucumber Holothuria moebii),⁹⁷⁶1343–1347 (starfish Echinaster luzonicus),⁹⁷⁷1348–1352 (sea cucumber Cercodemas anceps),⁹⁷⁸1353 (starfish Culcita novaeguineae),⁹⁷⁹1354 (sea cucumber Cucumaria japonica),⁹⁸⁰ and 1355–1362 (sea cucumber Cladolabes schmeltzii).⁹⁸¹

In addition to these MNPs, a further series of saponins (lessoniosides A–G) were reported from Holothuria lessoni.⁹⁸² As the structures were proposed based solely upon MSⁿ data, there are few data to define the associated aglycones and so the structures are not shown in this review. Using cladoloside C as a model (Cladolabes schmeltzii),⁹⁸³ chemical transformations combined with Moshers analysis has determined C-22 as having (R)-configuration.⁹⁸⁴ The authors speculated that all C-22 functionalised sea cucumber glycosides may have the same (22R) configuration. In an important development regarding the unambiguous characterisation of complex MNPs reported from echinoderms, the structures of gangliosides GAA-7 (ref. 985) (starfish Asterias amurensis)⁹⁸⁶ and PNG-2A⁹⁸⁷ (starfish Protoreaster nodosus)⁹⁸⁸ and steroidal glycosides astrosterioside A⁹⁸⁹ (starfish Astropecten monacanthus)⁹⁹⁰ and linkosides A and B⁹⁹¹ (starfish Linckia laevigata)⁹⁹² have been confirmed by total synthesis. Further studies using purified pentahydroxynaphthoquinone echinochrome A^993,994 have identified suppression of SERCA2A Ca²⁺ reuptake⁹⁹⁵ and improvement of exercise capacity in rats.⁹⁹⁶ A trisaccharide fragment of the starfish ganglioside LLG-3 (Linckia laevigata)⁹⁹⁷ promotes neurite extension in human neuroblastoma cells via MAPK/ERK signalling but not via Akt signalling.⁹⁹⁸ Polyhydroxylated sterols from the Vietnamese urchin Diadema savignyi induce apoptosis in HTCLs via inactivation of the MAPK/ERK1/2 pathway⁹⁹⁹ while sterols from the starfish Protoreaster nodosus were found to inhibit the production of pro-inflammatory cytokines including IL-12 p40, IL-6 and TNF-α in LPS-stimulated bone marrow-derived dendritic cells.¹⁰⁰⁰ Purified saponins from Chinese collections of Holothuria moebii exhibited in vitro cytotoxicity towards a panel of HTCLs and a total saponin fraction (mixture) inhibited CT-26 tumour growth in mice.¹⁰⁰¹ In a detailed study, the triterpene glycoside stichoposide D (Thelenota anax) was found to induce apoptosis in vitro in human leukemia cells through activation of CerS6 (ceramide synthase) and p38 kinase, and that similar activation properties were observed in vivo towards HL-60 and K562 xenografts.¹⁰⁰²

13 Mangroves

Mangroves or their associates were the sources of antiviral cyclohexylideneacetonitriles 1363–1366 (Bruguiera gymnorrhiza),¹⁰⁰³ a phenolic 1367 and a diol 1368 from the fruits of Avicennia marina,¹⁰⁰⁴ phenolics and a cerebroside 1369–1372 (Sonneratia ovata),¹⁰⁰⁵ glycosides 1373 (Kandelia candel)¹⁰⁰⁶ and 1374–1376 (Bruguiera gymnorrhiza),¹⁰⁰⁷seco-labdanoids 1377–1380 (Excoecaria agallocha),¹⁰⁰⁸ dolabrane-diterpenes 1381–1386 (Ceriops tagal),¹⁰⁰⁹ and limonoids 1387–1398 (ref. 1010) 1399–1401 (ref. 1011) (Xylocarpus moluccensis and X. granatum). The absolute configuration of the lignin rhamnoside 1376 was secured via analysis of experimental ECD data – the planar structure is identical to that of a previously reported metabolite of Cotoneaster racemiflora though with different magnitude and opposite sign of rotation.¹⁰¹² CD analysis and an X-ray study has led to the revision of the structure of rhizophorin A (Rhizophora mucronata)¹⁰¹³ to that shown for excolide A 1377.¹⁰⁰⁸ The structure of excolide B 1380 was also secured by X-ray analysis.

The absolute configurations of new limonoids, including thaixylomolins I 1389, K 1391 and M 1393, were determined by TD-DFT calculations of ECD data.¹⁰¹⁰ NMR data observed for 1391 were identical to those reported for the known phragmalin-skeletoned limonoid moluccensin J¹⁰¹⁴ – close examination of 2D NMR data requires structural correction of moluccensin J to structure 1391. Limonoids 1389, 1391 and 1393 exhibited mild anti-H1N1 viral activity. Further investigation of previously reported mangrove MNPs has identified the dolabrane-diterpene tagalsin C (Ceriops tagal)¹⁰¹⁵ to exhibit cytotoxicity in vitro towards a panel of haematologic cell lines, and in vivo towards human T-cell leukemia xenografts, via a mechanism involving ROS-mediated apoptosis and cell cycle arrest.¹⁰¹⁶ In addition the phenethyl cinnamide micrometam C (Micromelum falcatum)¹⁰¹⁷ protects against LPS-induced reactive oxygen species in both zebrafish and macrophages,¹⁰¹⁸ and limonoids xyloccensin E¹⁰¹⁹ and I¹⁰²⁰ (Xylocarpus moluccensis and X. granatum) exhibited anti-ulcer gastroprotective activities in rats, likely due to an ability to inhibit H⁺K⁺-ATPase activity.¹⁰²¹

14 Miscellaneous

A study of the sea grass Cymodocea serrulata has afforded an antibacterial constituent, which was attributed to the novel thiocarbonyl 1402.¹⁰²² The spectroscopic data reported for this compound are not however consistent with the proposed structure. A new member of the cephalostatin family, cephalostatin 20 1403, was isolated as a minor component of extracts of the marine worm Cephalodiscus gilchristi.¹⁰²³ Compared to the more potent members of the family (cephalostatins 1–3), cephalostatin 20 was 100–1000× less cytotoxic towards a panel of HTCLs. Efforts to reduce the structural complexity of the cephalostatins and to prepare analogues from the steroid hecogenin acetate resulted in compounds lacking any cytotoxic potency.¹⁰²⁴

Site-directed mutagenesis of the plasmid used for the heterologous expression of arenicin-1, an antimicrobial peptide produced by the polychaete worm Arenicola marina,¹⁰²⁵ afforded a number of analogues, one of which, Val8Arg, was equipotent as an antibacterial but with diminished red blood cell haemolytic activity.¹⁰²⁶ cDNA analysis of the venom gland of the sea snake Hydrophis cyanocinctus led to the identification of the first cathelicidin family antimicrobial peptide from a marine reptile.¹⁰²⁷ The peptide, Hc-CATH is a 30-mer and exhibits potent broad spectrum antimicrobial activity, via a mechanism related to membrane disruption and lysis. One critical step of the mechanism of light generation by cypridina luciferin, the luminescence precursor of the ostracod Cypridina (Vargula) hilgendorfii has been computationally modeled using structurally-simpler models.¹⁰²⁸ The peroxide intermediate cypridinid dioxetanone (CDO) can thermally decompose to generate excited oxyluciferin – CDO thermolysis via neutral or anionic forms were modeled, with the latter being found to be more energetically favourable in polar environments. The 33-amino-acid residue peptide pardaxin (flatfish Pardachirus marmoratus) exhibits in vitro and in vivo growth inhibition of oral squamous cell carcinoma.¹⁰²⁹ Mycosporine-like amino acids and gadusols are UV-vis protective compounds produced by a number of different species of marine organisms. Gadusol production in zebrafish is encoded by two gene products. By cloning into yeast yields of ∼20 mg L⁻¹ were obtained (5 days fermentation), opening the door to large scale production and use in commercial products.¹⁰³⁰

15 Conclusion

How things have changed over the past 45 years. In 1970 Professor G R Pettit made prophetic statements about the future for MNPs as a source of potential antineoplastic agents based on his widespread collections of marine vertebrates and invertebrates in 1968 along both coasts of North and South America and in Asia.¹⁰³¹ Through the years since he has published a myriad of papers that have confirmed his early convictions. Now, three sesquidecades on from that statement, the 600th paper in his series on antineoplastic agents has been published.¹⁰³² In this Conclusion we would like to acknowledge the outstanding contributions that he has made, and continues to make, to our field. In 1969 the remarkable antineoplastic properties of the ethanol/water extract from the ascidian Ecteinascidia turbinata were reported.¹⁰³³ Some years later the structures of the ecteinascidins were independently published^1034,1035 and ET-743, a bioactive research find, was transformed over the years to the anticancer drug Yondelis^® (trabectedin).¹⁰³⁶ In 2015 it was established that the producer of the ecteinascidins was the γ-proteobacterial endosymbiont Candidatus Endoecteinascidia frumentensis.²⁵ This example is characteristic of the changes that have taken place over the past 45 years in the foci of MNP research. Three other aspects of change will be examined in this Conclusion. Firstly, the type of organism collected. Fig. 1 shows the relative abundance of the most popular 15 phyla by sesquidecade from 1971. The less commonly collected organisms are grouped as Other.¹⁰³⁷ Right from the early days of MNPs the phylum Porifera has dominated. In the 1971–1985 sesquidecade the other phyla that were collected most avidly were the Cnidaria, Rhodophyta, Ochrophyta, Mollusca, and Echinodermata. The second sesquidecade from 1986–2000 was comparable, but marked the first appearance of the Ascomycota. In the third sesquidecade there were significant changes as the Ascomycota and Actinobacteria are now in the top four most widely collected phyla. In the coming sesquidecade from 2016–2030 microbially-derived compounds will almost certainly dominate the MNP field and this will be driven by factors such as the interest in the diversity of the microbial metabolites, the relative ease of collecting marine microbes from sediments, mud-flats, salterns or as endophytes from marine invertebrates, and the developing technologies for extraction of genomic material from microbes and its manipulation in heterologous systems.

Fig. 1 The most abundantly collected phyla by sesquidecade.

Research from Asian countries is now a dominant feature in MNP chemistry and was led from the start by Japan. This second aspect focuses on where the samples have been collected and in Fig. 2 the collection history of Japanese samples is examined over the three sesquidecades and compared with that of the newly emerging Asian groups collecting in Chinese, Taiwanese and South Korean waters. These collections from Asian waters now constitute about 30% of all compounds characterised and examination of Fig. 2 reveals that most of the collections from Chinese, Taiwanese and South Korean waters have taken place in the last sesquidecade with a very heavy emphasis placed on Cnidarian and microbial sources. Japanese collections have moved in that direction also, but still have a heavy emphasis on the phylum Porifera. Fig. 3 gives the perspective on the overall pattern of collections by phyla from 1971 to 2015.

Fig. 2 Collections in Japanese waters by sesquidecade contrasted with the collections in Chinese, Taiwanese and S. Korean waters.

Fig. 3 Distribution of the collection effort over the period 1971–2015 by phylum.

The third element of change examined is who we choose to publish with. This too has changed considerably over the years as some of the most popular journals for MNP publications were not available in 1971, or alternatively have lost favour or ceased publication. In Fig. 4 the 24 most popular journals overall (cut off <85) are compared on a sesquidecade basis. The Other category combines the output from a further 309 journals that have been used on at least one occasion through the years. The choice of journal in the first sesquidecade was quite different to the latter years with the Journal of Natural Products, Journal of Organic Chemistry, Tetrahedron, Tetrahedron Letters, Australian Journal of Chemistry and Phytochemistry emerging in the second sesquidecade. By the third sesquidecade Organic Letters and Marine Drugs had appeared and have been sought after as the journal of choice in addition to the Journal of Organic Chemistry, Tetrahedron, Tetrahedron Letters and most notably the Journal of Natural Products which has gone from strength to strength. As a proportion, however, more scientists are now publishing in the Other category.

Fig. 4 The 24 most selected journals used overall for publication of new compound data for the period 1971–2015, also shown by sesquidecade.

Year by year, little seems to change, but these three snapshots illustrate the actual magnitude of the changes that have occurred over the period that MNPs has been a discipline in its own right.

16 Acknowledgements

We thank Dr Helen Potter (Royal Society of Chemistry) for the provision of data used in this review, adapted from the MarinLit database with permission from the Royal Society of Chemistry.²⁴ This review is the fifteenth issue prepared by the New Zealand group of authors, and will be the last one contributed to by Professor Murray Munro, and we wish him all the best for his “retirement”. Professor Munro's contributions have been significant, particularly ensuring that the presentations from each of the authors of the various sections have had a similar style enabling a more consistent reading experience for readers of the review. He has also been responsible for the Conclusion section (15) in each review, providing insightful comment on a range of developments and trends in MNP research over several decades. The other authors are particularly grateful to Murray for his many contributions to these reviews, and other aspects of MNP research.

17 References

1. J. W. Blunt, B. R. Copp, R. A. Keyzers, M. H. G. Munro and M. R. Prinsep, Nat. Prod. Rep., 2016, 33, 382–431,  10.1039/c5np00156k.
2. J. W. Blunt, B. R. Copp, R. A. Keyzers, M. H. G. Munro and M. R. Prinsep, Nat. Prod. Rep., 2015, 32, 116–211,  10.1039/c4np00144c.
3. Y. Hu, J. Chen, G. Hu, J. Yu, X. Zhu, Y. Lin, S. Chen and J. Yuan, Mar. Drugs, 2015, 13, 202–221,  DOI:10.3390/md13010202.
4. V. Gogineni, R. F. Schinazi and M. T. Hamann, Chem. Rev., 2015, 115, 9655–9706,  DOI:10.1021/cr4006318.
5. N. Gomes, F. Lefranc, A. Kijjoa and R. Kiss, Mar. Drugs, 2015, 13, 3950–3991,  DOI:10.3390/md13063950.
6. L. Xu, W. Meng, C. Cao, J. Wang, W. Shan and Q. Wang, Mar. Drugs, 2015, 13, 3479–3513,  DOI:10.3390/md13063479.
7. S. Moghadamtousi, S. Nikzad, H. Kadir, S. Abubakar and K. Zandi, Mar. Drugs, 2015, 13, 4520–4538,  DOI:10.3390/md13074520.
8. J. Ye, F. Zhou, A. M. Q. Al-Kareef and H. Wang, J. Asian Nat. Prod. Res., 2015, 17, 64–88,  DOI:10.1080/10286020.2014.970535.
9. E. Talero, S. García-Mauriño, J. Ávila-Román, A. Rodríguez-Luna, A. Alcaide and V. Motilva, Mar. Drugs, 2015, 13, 6152–6209,  DOI:10.3390/md13106152.
10. H. Kang, C. Seo and Y. Park, Mar. Drugs, 2015, 13, 618–654,  DOI:10.3390/md13010618.
11. R. Cheung, T. Ng and J. Wong, Mar. Drugs, 2015, 13, 4006–4043,  DOI:10.3390/md13074006.
12. Z.-F. Zhou, M. Menna, Y.-S. Cai and Y.-W. Guo, Chem. Rev., 2015, 115, 1543–1596,  DOI:10.1021/cr4006507.
13. N. Netz and T. Opatz, Mar. Drugs, 2015, 13, 4814–4914,  DOI:10.3390/md13084814.
14. G. Gribble, Mar. Drugs, 2015, 13, 4044–4136,  DOI:10.3390/md13074044.
15. Y. Sharifuddin, Y.-X. Chin, P.-E. Lim and S.-M. Phang, Mar. Drugs, 2015, 13, 5447–5491,  DOI:10.3390/md13085447.
16. D.-Y. Choi and H. Choi, Arch. Pharmacal Res., 2015, 38, 139–170,  DOI:10.1007/s12272-014-0503-5.
17. P.-Y. Qian, Z. Li, Y. Xu, Y. Li and N. Fusetani, Biofouling, 2015, 31, 101–122,  DOI:10.1080/08927014.2014.997226.
18. L. A. Salvador-Reyes and H. Luesch, Nat. Prod. Rep., 2015, 32, 478–503,  10.1039/c4np00104d.
19. P. R. Jensen, B. S. Moore and W. Fenical, Nat. Prod. Rep., 2015, 32, 738–751,  10.1039/c4np00167b.
20. M. Trindade, L. J. van Zyl, J. Navarro-Fernández and A. A. Elrazak, Front. Microbiol., 2015, 6, 890,  DOI:10.3389/fmicb.2015.00890.
21. F. Jerry Reen, S. Romano, A. D. W. Dobson and F. O'Gara, Mar. Drugs, 2015, 13, 4754–4783,  DOI:10.3390/md13084754.
22. F. Reen, J. Gutiérrez-Barranquero, A. Dobson, C. Adams and F. O'Gara, Mar. Drugs, 2015, 13, 2924–2954,  DOI:10.3390/md13052924.
23. K. Li, Y.-W. Chung-Davidson, U. Bussy and W. Li, Mar. Drugs, 2015, 13, 2694–2713,  DOI:10.3390/md13052694.
24. http://pubs.rsc.org/marinlit, accessed December 2016.
25. M. M. Schofield, S. Jain, D. Porat, G. J. Dick and D. H. Sherman, Environ. Microbiol., 2015, 17, 3964–3975,  DOI:10.1111/1462–2920.12908.
26. E. Ju Choi, S.-J. Nam, L. Paul, D. Beatty, C. A. Kauffman, P. R. Jensen and W. Fenical, Chem. Biol., 2015, 22, 1270–1279,  DOI:10.1016/j.chembiol.2015.07.014.
27. D. Liu, H. Lin, P. Proksch, X. Tang, Z. Shao and W. Lin, Org. Lett., 2015, 17, 1220–1223,  DOI:10.1021/acs.orglett.5b00172.
28. C. J. Schulze, M. S. Donia, J. L. Siqueira-Neto, D. Ray, J. A. Raskatov, R. E. Green, J. H. McKerrow, M. A. Fischbach and R. G. Linington, ACS Chem. Biol., 2015, 10, 2373–2381,  DOI:10.1021/acschembio.5b00308.
29. M. Land, A. Lapidus, S. Mayilraj, F. Chen, A. Copeland, T. G. Del Rio, M. Nolan, S. Lucas, H. Tice, J.-F. Cheng, O. Chertkov, D. Bruce, L. Goodwin, S. Pitluck, M. R. M. Göker, A. Pati, N. Ivanova, K. Mavromatis, A. Chen, K. Palaniappan, L. Hauser, Y. J. Chang, C. C. Jeffries, T. Brettin, J. C. Detter, C. Han, P. Chain, B. J. Tindall, J. Bristow, J. A. Eisen, V. Markowitz, P. Hugenholtz, N. C. Kyrpides and H.-P. Klenk, Stand. Genomic Sci., 2009, 1, 46–53,  DOI:10.4056/sigs.21137.
30. W. Zhang, Z. Liu, S. Li, Y. Lu, Y. Chen, H. Zhang, G. Zhang, Y. Zhu, G. Zhang, W. Zhang, J. Li and C. Zhang, J. Nat. Prod., 2012, 75, 1937–1943,  DOI:10.1021/np300505y.
31. C. Yang, C. Huang, W. Zhang, Y. Zhu and C. Zhang, Org. Lett., 2015, 17, 5324–5327,  DOI:10.1021/acs.orglett.5b02683.
32. M. W. Mullowney, E. Ó hAinmhire, U. Tanouye, J. E. Burdette, V. C. Pham and B. T. Murphy, Mar. Drugs, 2015, 13, 5815–5827,  DOI:10.3390/md13095815.
33. N. Adnani, E. Vazquez-Rivera, S. Adibhatla, G. Ellis, D. Braun and T. Bugni, Mar. Drugs, 2015, 13, 6082–6098,  DOI:10.3390/md13106082.
34. A. S. Leutou, I. Yang, H. Kang, E. K. Seo, S.-J. Nam and W. Fenical, J. Nat. Prod., 2015, 78, 2846–2849,  DOI:10.1021/acs.jnatprod.5b00746.
35. S. Takase, M. Iwami, T. Ando, M. Okamoto, K. Kohsaka, H. Aoki and H. Imanaka, J. Antibiot., 1984, 37, 1320–1323,  DOI:10.7164/antibiotics.37.1320.
36. W.-B. Yin, X.-L. Xie, M. Matuschek and S.-M. Li, Org. Biomol. Chem., 2010, 8, 1133–1141,  10.1039/b922440h.
37. K. Kobayashi, T. Fukuda, T. Terahara, E. Harunari, C. Imada and H. Tomoda, J. Antibiot., 2015, 68, 638–641,  DOI:10.1038/ja.2015.38.
38. J. L. Li, L. Huang, J. Liu, Y. Song, J. Gao, J. H. Jung, Y. Liu and G. Chen, Fitoterapia, 2015, 102, 203–207,  DOI:10.1016/j.fitote.2015.01.014.
39. M. Gan, B. Liu, Y. Tan, Q. Wang, H. Zhou, H. He, Y. Ping, Z. Yang, Y. Wang and C. Xiao, J. Nat. Prod., 2015, 78, 2260–2265,  DOI:10.1021/acs.jnatprod.5b00577.
40. K. R. Duncan, M. Crüsemann, A. Lechner, A. Sarkar, J. Li, N. Ziemert, M. Wang, N. Bandeira, B. S. Moore, P. C. Dorrestein and P. R. Jensen, Chem. Biol., 2015, 22, 460–471,  DOI:10.1016/j.chembiol.2015.03.010.
41. T. K. S. Richter, C. C. Hughes and B. S. Moore, Environ. Microbiol., 2015, 17, 2158–2171,  DOI:10.1111/1462–2920.12669.
42. B. Bonet, R. Teufel, M. Crüsemann, N. Ziemert and B. S. Moore, J. Nat. Prod., 2015, 78, 539–542,  DOI:10.1021/np500664q.
43. C. J. Schulze, G. Navarro, D. Ebert, J. DeRisi and R. G. Linington, J. Org. Chem., 2015, 80, 1312–1320,  DOI:10.1021/jo5024409.
44. S. J. Nam, C. A. Kauffman, P. R. Jensen and W. Fenical, Tetrahedron, 2011, 67, 6707–6712,  DOI:10.1016/j.tet.2011.04.051.
45. D. E. Williams, D. S. Dalisay, B. O. Patrick, T. Matainaho, K. Andrusiak, R. Deshpande, C. L. Myers, J. S. Piotrowski, C. Boone, M. Yoshida and R. J. Andersen, Org. Lett., 2011, 13, 3936–3939,  DOI:10.1021/ol2014494.
46. K. C.-C. Cheng, S. Cao, A. Raveh, R. MacArthur, P. Dranchak, G. Chlipala, M. T. Okoneski, R. Guha, R. T. Eastman, J. Yuan, P. J. Schultz, X.-z. Su, G. Tamayo-Castillo, T. Matainaho, J. Clardy, D. H. Sherman and J. Inglese, J. Nat. Prod., 2015, 78, 2411–2422,  DOI:10.1021/acs.jnatprod.5b00489.
47. Z. D. Jiang, P. R. Jensen and W. Fenical, Bioorg. Med. Chem. Lett., 1999, 9, 2003–2006,  DOI:10.1016/S0960-894X(99)00337-6.
48. R. B. Wei, T. Xi, J. Li, P. Wang, F. C. Li, Y. C. Lin and S. Qin, Mar. Drugs, 2011, 9, 359–368,  DOI:10.3390/md9030359.
49. S. Niu, S. Li, Y. Chen, X. Tian, H. Zhang, G. Zhang, W. Zhang, X. Yang, S. Zhang, J. Ju and C. Zhang, J. Antibiot., 2011, 64, 711–716,  DOI:10.1038/ja.2011.78.
50. H. Q. Pan, S. Y. Zhang, N. Wang, Z. L. Li, H. M. Hua, J. C. Hu and S. J. Wang, Mar. Drugs, 2013, 11, 3891–3901,  DOI:10.3390/md11103891.
51. P. G. Cruz, A. M. Fribley, J. R. Miller, M. J. Larsen, P. J. Schultz, R. T. Jacob, G. Tamayo-Castillo, R. J. Kaufman and D. H. Sherman, ACS Med. Chem. Lett., 2015, 6, 877–881,  DOI:10.1021/acsmedchemlett.5b00127.
52. Q. Li, Y. Song, X. Qin, X. Zhang, A. Sun and J. Ju, J. Nat. Prod., 2015, 78, 944–948,  DOI:10.1021/acs.jnatprod.5b00009.
53. H. M. Hassan, D. Degen, K. H. Jang, R. H. Ebright and W. Fenical, J. Antibiot., 2015, 68, 206–209,  DOI:10.1038/ja.2014.122.
54. F. Zhang, N. Adnani, E. Vazquez-Rivera, D. R. Braun, M. Tonelli, D. R. Andes and T. S. Bugni, J. Org. Chem., 2015, 80, 8713–8719,  DOI:10.1021/acs.joc.5b01486.
55. Y.-N. Song, W.-J. Zhang, S.-F. Bi, R.-H. Jiao, R.-X. Tan and H.-M. Ge, J. Antibiot., 2015, 68, 757–759,  DOI:10.1038/ja.2015.65.
56. K. Jomon, Y. Kuroda, M. Ajisaka and H. Sakai, J. Antibiot., 1972, 25, 271–280,  DOI:10.7164/antibiotics.25.271.
57. R. Lacret, D. Oves-Costales, C. Gómez, C. Díaz, M. de la Cruz, I. Pérez-Victoria, F. Vicente, O. Genilloud and F. Reyes, Mar. Drugs, 2015, 13, 128–140,  DOI:10.3390/md13010128.
58. C. Gui, Q. Li, X. Mo, X. Qin, J. Ma and J. Ju, Org. Lett., 2015, 17, 628–631,  DOI:10.1021/ol5036497.
59. X. Zhen, T. Gong, F. Liu, P.-C. Zhang, W.-Q. Zhou, Y. Li and P. Zhu, Mar. Drugs, 2015, 13, 6947–6961,  DOI:10.3390/md13116947.
60. K. Kobayashi, T. Fukuda, T. Usui, Y. Kurihara, A. Kanamoto and H. Tomoda, J. Antibiot., 2015, 68, 126–132,  DOI:10.1038/ja.2014.100.
61. N. Liu, F. Song, F. Shang and Y. Huang, Mar. Drugs, 2015, 13, 6247–6258,  DOI:10.3390/md13106247.
62. S.-J. Nam, C. A. Kauffman, P. R. Jensen, C. E. Moore, A. L. Rheingold and W. Fenical, Org. Lett., 2015, 17, 3240–3243,  DOI:10.1021/acs.orglett.5b01387.
63. P. Fu and J. B. MacMillan, Org. Lett., 2015, 17, 3046–3049,  DOI:10.1021/acs.orglett.5b01328.
64. S.-M. Zhang, H.-Y. Zhang, S.-X. Yang, C.-L. Qu, Z.-P. Xie and G. Pescitelli, Chirality, 2015, 27, 82–87,  DOI:10.1002/chir.22393.
65. Y. Song, G. Liu, J. Li, H. Huang, X. Zhang, H. Zhang and J. Ju, Mar. Drugs, 2015, 13, 1304–1316,  DOI:10.3390/md13031304.
66. J. Vicente, A. K. Stewart, R. M. van Wagoner, E. Elliott, A. J. Bourdelais and J. L. C. Wright, Mar. Drugs, 2015, 13, 4682–4700,  DOI:10.3390/md13084682.
67. Z. G. Khalil, R. Raju, A. M. Piggott, A. A. Salim, A. Blumenthal and R. J. Capon, J. Nat. Prod., 2015, 78, 949–952,  DOI:10.1021/acs.jnatprod.5b00095.
68. A. Reimer, A. Blohm, T. Quack, C. G. Grevelding, V. Kozjak-Pavlovic, T. Rudel, U. Hentschel and U. R. Abdelmohsen, J. Antibiot., 2015, 68, 674–679,  DOI:10.1038/ja.2015.54.
69. G. R. Pettit, R. Tan, R. K. Pettit, D. L. Doubek, J.-C. Chapuis and C. A. Weber, RSC Adv., 2015, 5, 9116–9122,  10.1039/c4ra16517a.
70. J. Riedlinger, A. Reicke, H. Zahner, B. Krismer, A. T. Bull, L. A. Maldonado, A. C. Ward, M. Goodfellow, B. Bister, D. Bischoff, R. D. Süssmuth and H.-P. Fiedler, J. Antibiot., 2004, 57, 271–279,  DOI:10.7164/antibiotics.57.271.
71. Y. Igarashi, L. Yu, S. Miyanaga, T. Fukuda, N. Saitoh, H. Sakurai, I. Saiki, P. Alonso-Vega and M. E. Trujillo, J. Nat. Prod., 2010, 73, 1943–1946,  DOI:10.1021/np100292h.
72. B. León, G. Navarro, B. J. Dickey, G. Stepan, A. Tsai, G. S. Jones, M. E. Morales, T. Barnes, S. Ahmadyar, M. Tsiang, R. Geleziunas, T. Cihlar, N. Pagratis, Y. Tian, H. Yu and R. G. Linington, Org. Lett., 2015, 17, 262–265,  DOI:10.1021/ol503349y.
73. Y. Igarashi, M. Ikeda, S. Miyanaga, H. Kasai, Y. Shizuri and N. Matsuura, J. Antibiot., 2015, 68, 345–347,  DOI:10.1038/ja.2014.151.
74. D. Yang, Q. Y. Xu, X. M. Deng, S. Y. Song, Z. Y. Hu and Z. H. Zheng, Rec. Nat. Prod., 2015, 9, 336–341.
75. S. Guo, H. Su, X. Li, D. Shi and X. Zhu, Chem. Nat. Compd., 2015, 51, 480–482,  DOI:10.1007/s10600-015-1319-3.
76. A. S. Leutou, I. Yang, C. N. Seong, J. Ko and S.-J. Nam, Nat. Prod. Sci., 2015, 21, 248–250,  DOI:10.20307/nps.2015.21.4.248.
77. B. Shin, S. Ahn, M. Noh, J. Shin and D.-C. Oh, J. Nat. Prod., 2015, 78, 1390–1396,  DOI:10.1021/acs.jnatprod.5b00284.
78. D. Thirumurugan and R. Vijayakumar, Curr. Microbiol., 2015, 70, 745–755,  DOI:10.1007/s00284-015-0780-3.
79. X. An, B. Zhang, H. Zhang, Y. Li, W. Zheng, Z. Yu, L. Fu and T. Zheng, Front. Microbiol., 2015, 6, 1235,  DOI:10.3389/fmicb.2015.01235.
80. J. Shanthi, A. Senthil, V. Gopikrishnan and R. Balagurunathan, Appl. Biochem. Biotechnol., 2015, 175, 3696–3708,  DOI:10.1007/s12010-015-1538-x.
81. F. Strelitz, H. Flon and I. N. Asheshov, Proc. Natl. Acad. Sci. U. S. A., 1955, 41, 620–624.
82. M. Arai, K. Kamiya, P. Pruksakorn, Y. Sumii, N. Kotoku, J.-P. Joubert, P. Moodley, C. Han, D. Shin and M. Kobayashi, Bioorg. Med. Chem., 2015, 23, 3534–3541,  DOI:10.1016/j.bmc.2015.04.033.
83. R. Raju, A. M. Piggott, M. Conte, W. G. L. Aalbersberg, K. Feussner and R. J. Capon, Org. Lett., 2009, 11, 3862–3865,  DOI:10.1021/ol901466r.
84. Z.-Q. Xiong, Q.-X. Liu, Z.-L. Pan, N. Zhao, Z.-X. Feng and Y. Wang, Arch. Microbiol., 2015, 197, 299–309,  DOI:10.1007/s00203-014-1059-y.
85. L. Harinantenaina Rakotondraibe, R. Rasolomampianina, H.-Y. Park, J. Li, C. Slebodnik, P. J. Brodie, L. C. Blasiak, R. Hill, K. TenDyke, Y. Shen, M. B. Cassera, F. Rejo and D. G. I. Kingston, Bioorg. Med. Chem. Lett., 2015, 25, 5646–5649,  DOI:10.1016/j.bmcl.2015.07.103.
86. F. S. Tareq, H.-S. Lee, Y.-J. Lee, J. S. Lee and H. J. Shin, Lipids, 2015, 50, 513–519,  DOI:10.1007/s11745-015-4014-z.
87. F. S. Tareq, C. M. Hasan, H.-S. Lee, Y.-J. Lee, J. S. Lee, M. Z. Surovy, M. Tofazzal Islam and H. J. Shin, Bioorg. Med. Chem. Lett., 2015, 25, 3325–3329,  DOI:10.1016/j.bmcl.2015.05.070.
88. A. I. M. Khedr, G. A. Mohamed, M. A. A. Orabi, S. R. M. Ibrahim and K. Yamada, Phytochem. Lett., 2015, 13, 11–14,  DOI:10.1016/j.phytol.2015.05.007.
89. http://au.wiley.com/WileyCDA/WileyTitle/productCd-3527338411.html, accessed, December 2016.
90. C.-C. Liaw, P.-C. Chen, C.-J. Shih, S.-P. Tseng, Y.-M. Lai, C.-H. Hsu, P. C. Dorrestein and Y.-L. Yang, Sci. Rep., 2015, 5, 12856,  DOI:10.1038/srep12856.
91. C. M. Theodore, N. Lorig-Roach, P. C. Still, T. A. Johnson, M. Drašković, J. A. Schwochert, C. N. Naphen, M. S. Crews, S. A. Barker, F. A. Valeriote, R. Scott Lokey and P. Crews, J. Nat. Prod., 2015, 78, 441–452,  DOI:10.1021/np500840n.
92. F. Can Özkaya, E. Bedir and E. Esin Hameş, Rec. Nat. Prod., 2015, 9, 509–517.
93. S. Carillo, A. Casillo, G. Pieretti, E. Parrilli, F. Sannino, M. Bayer-Giraldi, S. Cosconati, E. Novellino, M. Ewert, J. W. Deming, R. Lanzetta, G. Marino, M. Parrilli, A. Randazzo, M. L. Tutino and M. Michela Corsaro, J. Am. Chem. Soc., 2015, 137, 179–189,  DOI:10.1021/ja5075954.
94. L. Ding, J. Munich, H. Goerls, A. Maier, H. H. Fiebig, W. H. Lin and C. Hertweck, Bioorg. Med. Chem. Lett., 2010, 20, 6685–6687,  DOI:10.1016/j.bmcl.2010.09.010.
95. L. Ding, A. Maier, H. H. Fiebig, W. H. Lin and C. Hertweck, Org. Biomol. Chem., 2011, 9, 4029–4031,  10.1039/c1ob05283g.
96. M. Baunach, L. Ding, K. Willing and C. Hertweck, Angew. Chem., Int. Ed., 2015, 54, 13279–13283,  DOI:10.1002/anie.201506541.
97. H. Li, Y. Sun, Q. Zhang, Y. Zhu, S.-M. Li, A. Li and C. Zhang, Org. Lett., 2015, 17, 306–309,  DOI:10.1021/ol503399b.
98. L. Ding, H. Goerls, K. Dornblut, W. Lin, A. Maier, H.-H. Fiebig and C. Hertweck, J. Nat. Prod., 2015, 78, 2963–2967,  DOI:10.1021/acs.jnatprod.5b00674.
99. L. Ding, A. Maier, H. H. Fiebig, H. Gorls, W. H. Lin, G. Peschel and C. Hertweck, Angew. Chem., Int. Ed., 2011, 50, 1630–1634,  DOI:10.1002/anie.201006165.
100. L. Ding, J. Franke and C. Hertweck, Org. Biomol. Chem., 2015, 13, 1618–1623,  10.1039/c4ob02244k.
101. P. Fu and J. B. MacMillan, J. Nat. Prod., 2015, 78, 548–551,  DOI:10.1021/np500929z.
102. T. Nakashima, Y. Kamiya, M. Iwatsuki, N. Sato, Y. Takahashi and Satoshi Ōmura, J. Antibiot., 2015, 68, 220–222,  DOI:10.1038/ja.2014.134.
103. S. Noguchi, Z. Yamaizumi, T. Ohgi, T. Goto, Y. Nishimura, Y. Hirota and S. Nishimura, Nucleic Acids Res., 1978, 5, 4215–4224,  DOI:10.1093/nar/5.11.4215.
104. D. Xu, M. Ma, Y. Liu, T. Zhou, K. Wang, Z. Deng and K. Hong, Anti-Cancer Agents Med. Chem., 2015, 15, 285–290,  DOI:10.2174/1871520614666141027144653.
105. H. Huang, X. Lan, Y. Wang, L. Tian, Y. Fang, L. Zhang, K. Zhang and X. Zheng, Phytochem. Lett., 2015, 12, 190–195,  DOI:10.1016/j.phytol.2015.04.001.
106. E. Rossner, A. Zeeck and W. A. Konig, Angew. Chem., Int. Ed., 1990, 29, 64–65,  DOI:10.1002/anie.199000641.
107. M. Bae, B. Chung, K.-B. Oh, J. Shin and D.-C. Oh, Mar. Drugs, 2015, 13, 5187–5200,  DOI:10.3390/md13085187.
108. M. Bae, H. Kim, K. Moon, S.-J. Nam, J. Shin, K.-B. Oh and D.-C. Oh, Org. Lett., 2015, 17, 712–715,  DOI:10.1021/ol5037248.
109. K. Moon, B. Chung, Y. Shin, A. L. Rheingold, C. E. Moore, S. J. Park, S. Park, S. K. Lee, K.-B. Oh, J. Shin and D.-C. Oh, J. Nat. Prod., 2015, 78, 524–529,  DOI:10.1021/np500736b.
110. S.-H. Kim, Y. Shin, S.-H. Lee, K.-B. Oh, S. K. Lee, J. Shin and D.-C. Oh, J. Nat. Prod., 2015, 78, 836–843,  DOI:10.1021/acs.jnatprod.5b00002.
111. S.-H. Kim, Y. Shin, S. K. Lee, J. Shin and D.-C. Oh, Nat. Prod. Sci., 2015, 21, 273–277,  DOI:10.20307/nps.2015.21.4.273.
112. M. C. Kim, J. H. Lee, B. Shin, L. Subedi, J. W. Cha, J.-S. Park, D.-C. Oh, S. Y. Kim and H. C. Kwon, Org. Lett., 2015, 17, 5024–5027,  DOI:10.1021/acs.orglett.5b02495.
113. X. Zhou, H. Huang, Y. Chen, J. Tan, Y. Song, J. Zou, X. Tian, Y. Hua and J. Ju, J. Nat. Prod., 2012, 75, 2251–2255,  DOI:10.1021/np300554f.
114. Y. Zhang, M. A. Islam and S. R. McAlpine, Org. Lett., 2015, 17, 5149–5151,  DOI:10.1021/acs.orglett.5b02574.
115. T. P. Wyche, Y. Hou, D. Braun, H. C. Cohen, M. P. Xiong and T. S. Bugni, J. Org. Chem., 2011, 76, 6542–6547,  DOI:10.1021/jo200661n.
116. M. R. Vippila, P. K. Ly and G. D. Cuny, J. Nat. Prod., 2015, 78, 2398–2404,  DOI:10.1021/acs.jnatprod.5b00428.
117. T. Barsby, M. T. Kelly, S. M. Gagne and R. J. Andersen, Org. Lett., 2001, 3, 437–440,  DOI:10.1021/ol006942q.
118. T. Yamashita, T. Kuranaga and M. Inoue, Org. Lett., 2015, 17, 2170–2173,  DOI:10.1021/acs.orglett.5b00769.
119. J. M. Vraspir, P. D. Holt and A. Butler, BioMetals, 2011, 24, 85–92,  DOI:10.1007/s10534-010-9378-1.
120. J. M. Gauglitz and A. Butler, J. Biol. Inorg Chem., 2013, 18, 489–497,  DOI:10.1007/s00775-013-0995-3.
121. P. Cherkupally, S. Ramesh, T. Govender, H. G. Kruger, B. G. de la Torre and F. Albericio, Org. Biomol. Chem., 2015, 13, 4760–4768,  10.1039/c5ob00100e.
122. P. Fu, Y. B. Zhuang, Y. Wang, P. P. Liu, X. Qi, K. B. Gu, D. J. Zhang and W. M. Zhu, Org. Lett., 2012, 14, 6194–6197,  DOI:10.1021/ol302940y.
123. L. Wang, X. Mei, C. Wang and W. Zhu, Tetrahedron, 2015, 71, 7990–7997,  DOI:10.1016/j.tet.2015.08.065.
124. S. Omura, Y. Iwai, A. Hirano, A. Nakagawa, J. Awaya, H. Tsuchiya, Y. Takahashi and R. Masuma, J. Antibiot., 1977, 30, 275–282,  DOI:10.7164/antibiotics.30.275.
125. A. Yang, L. Si, Z. Shi, L. Tian, D. Liu, D. Zhou, P. Proksch and W. Lin, Org. Lett., 2013, 15, 5366–5369,  DOI:10.1021/ol4026809.
126. S. C. Philkhana, G. R. Jachak, V. B. Gunjal, N. M. Dhage, A. H. Bansode and D. S. Reddy, Tetrahedron Lett., 2015, 56, 1252–1254,  DOI:10.1016/j.tetlet.2015.01.143.
127. S. J. Nam, S. P. Gaudencio, C. A. Kauffman, P. R. Jensen, T. P. Kondratyuk, L. E. Marler, J. M. Pezzuto and W. Fenical, J. Nat. Prod., 2010, 73, 1080–1086,  DOI:10.1021/np100087c.
128. C. Heinz and N. Cramer, J. Am. Chem. Soc., 2015, 137, 11278–11281,  DOI:10.1021/jacs.5b07964.
129. H. C. Kwon, C. A. Kauffman, P. R. Jensen and W. Fenical, J. Org. Chem., 2009, 74, 675–684,  DOI:10.1021/jo801944d.
130. L. C. Dias and E. C. de Lucca, Org. Lett., 2015, 17, 6278–6281,  DOI:10.1021/acs.orglett.5b03352.
131. W. K. Strangman, H. C. Kwon, D. Broide, P. R. Jensen and W. Fenical, J. Med. Chem., 2009, 52, 2317–2327,  DOI:10.1021/jm801110j.
132. K.-i. Yoshida, M. Ijiri, H. Iio and Y. Usuki, Tetrahedron, 2015, 71, 9626–9629,  DOI:10.1016/j.tet.2015.10.075.
133. U. W. Hawas, M. Shaaban, K. A. Shaaban, M. Speitling, A. Maier, G. Kelter, H. H. Fiebig, M. Meiners, E. Helmke and H. Laatsch, J. Nat. Prod., 2009, 72, 2120–2124,  DOI:10.1021/np900160g.
134. A. Coppola, D. Sucunza, C. Burgos and J. J. Vaquero, Org. Lett., 2015, 17, 78–81,  DOI:10.1021/ol5032624.
135. R. Raju, A. M. Piggott, L. X. B. Diaz, Z. Khalil and R. J. Capon, Org. Lett., 2010, 12, 5158–5161,  DOI:10.1021/ol102162d.
136. T. Matsuo, S. Hashimoto, K. Nishikawa, T. Kodama, S. Kikuchi, Y. Tachi and Y. Morimoto, Tetrahedron Lett., 2015, 56, 5345–5348,  DOI:10.1016/j.tetlet.2015.07.094.
137. A. M. Socha, R. A. Long and D. C. Rowley, J. Nat. Prod., 2007, 70, 1793–1795,  DOI:10.1021/np070126a.
138. X. Sun, Y. Liu, J. Liu, G. Gu and Y. Du, Org. Biomol. Chem., 2015, 13, 4271–4277,  10.1039/c5ob00093a.
139. G. D. A. Martin, L. T. Tan, P. R. Jensen, R. E. Dimayuga, C. R. Fairchild, C. Raventos-Suarez and W. Fenical, J. Nat. Prod., 2007, 70, 1406–1409,  DOI:10.1021/np060621r.
140. T. Cañeque, F. Gomes, T. T. Mai, G. Maestri, M. Malacria and R. Rodriguez, Nat. Chem., 2015, 7, 744–751,  DOI:10.1038/nchem.2302.
141. X. Alvarez-Mico, P. R. Jensen, W. Fenical and C. C. Hughes, Org. Lett., 2013, 15, 988–991,  DOI:10.1021/ol303374e.
142. X. Álvarez-Micó, D. D. Rocha, L. A. Guimarães, A. Ambrose, E. Chapman, L. V. Costa-Lotufo, J. J. La Clair and W. Fenical, ChemBioChem, 2015, 16, 2002–2006,  DOI:10.1002/cbic.201500229.
143. D. C. Oh, W. K. Strangman, C. A. Kauffman, P. R. Jensen and W. Fenical, Org. Lett., 2007, 9, 1525–1528,  DOI:10.1021/ol070294u.
144. L. Lu, M. J. Meehan, S. Gu, Z. Chen, W. Zhang, G. Zhang, L. Liu, X. Huang, P. C. Dorrestein, Y. Xu, B. S. Moore and P.-Y. Qian, Sci. Rep., 2015, 5, 8783,  DOI:10.1038/srep08783.
145. Y. Igarashi, T. Zhou, S. Sato, T. Matsumoto, L. Yu and N. Oku, Org. Lett., 2013, 15, 5678–5681,  DOI:10.1021/ol402661r.
146. F. Iwata, S. Sato, T. Mukai, S. Yamada, J. Takeo, A. Abe, T. Okita and H. Kawahara, J. Nat. Prod., 2009, 72, 2046–2048,  DOI:10.1021/np900353y.
147. T. Zhou, H. Komaki, N. Ichikawa, A. Hosoyama, S. Sato and Y. Igarashi, Mar. Drugs, 2015, 13, 581–596,  DOI:10.3390/md13010581.
148. X. Zhou, H. Huang, J. Li, Y. Song, R. Jiang, J. Liu, S. Zhang, Y. Hua and J. Ju, Tetrahedron, 2014, 70, 7795–7801,  DOI:10.1016/j.tet.2014.02.007.
149. J. Liu, B. Wang, H. Li, Y. Xie, Q. Li, X. Qin, X. Zhang and J. Ju, Org. Lett., 2015, 17, 1509–1512,  DOI:10.1021/acs.orglett.5b00389.
150. R. Raju, A. M. Piggott, M. M. Conte and R. J. Capon, Org. Biomol. Chem., 2010, 8, 4682–4689,  10.1039/c0ob00267d.
151. Y. Zhu, W. Zhang, Y. Chen, C. Yuan, H. Zhang, G. Zhang, L. Ma, Q. Zhang, X. Tian, S. Zhang and C. Zhang, ChemBioChem, 2015, 16, 2086–2093,  DOI:10.1002/cbic.201500281.
152. P. Yu, A. Patel and K. N. Houk, J. Am. Chem. Soc., 2015, 137, 13518–13523,  DOI:10.1021/jacs.5b06656.
153. K. H. Jang, S. J. Nam, J. B. Locke, C. A. Kauffman, D. S. Beatty, L. A. Paul and W. Fenical, Angew. Chem., Int. Ed., 2013, 52, 7822–7824,  DOI:10.1002/anie.201302749.
154. K. H. Jang, S.-J. Nam, J. B. Locke, C. A. Kauffman, D. S. Beatty, L. A. Paul and W. Fenical, Angew. Chem., Int. Ed., 2014, 53, 621,  DOI:10.1002/anie.201310144.
155. K. Gerth, H. Steinmetz, G. Höfle and R. Jansen, Angew. Chem., Int. Ed., 2008, 47, 600–602,  DOI:10.1002/anie.200703993.
156. S. Alt and B. Wilkinson, ACS Chem. Biol., 2015, 10, 2468–2479,  DOI:10.1021/acschembio.5b00525.
157. K. Jungmann, R. Jansen, K. Gerth, V. Huch, D. Krug, W. Fenical and R. Müller, ACS Chem. Biol., 2015, 10, 2480–2490,  DOI:10.1021/acschembio.5b00523.
158. D.-C. Oh, E. A. Gontang, C. A. Kauffman, P. R. Jensen and W. Fenical, J. Nat. Prod., 2008, 71, 570–575,  DOI:10.1021/np0705155.
159. Y. Iizaka, N. Higashi, M. Ishida, R. Oiwa, Y. Ichikawa, M. Takeda, Y. Anzai and F. Kato, Antimicrob. Agents Chemother., 2013, 57, 1529–1531,  DOI:10.1128/AAC.02092-12.
160. G. H. Wagman, J. A. Waitz, J. Marquez, A. Murawski, E. M. Oden, R. T. Testa and M. J. Weinstein, J. Antibiot., 1972, 25, 641–646,  DOI:10.7164/antibiotics.25.641.
161. T. Awakawa, M. Crüsemann, J. Munguia, N. Ziemert, V. Nizet, W. Fenical and B. S. Moore, ChemBioChem, 2015, 16, 1443–1447,  DOI:10.1002/cbic.201500177.
162. C. Chang, R. Huang, Y. Yan, H. Ma, Z. Dai, B. Zhang, Z. Deng, W. Liu and X. Qu, J. Am. Chem. Soc., 2015, 137, 4183–4190,  DOI:10.1021/jacs.5b00728.
163. R. Raju, A. M. Piggott, X. C. Huang and R. J. Capon, Org. Lett., 2011, 13, 2770–2773,  DOI:10.1021/ol200904v.
164. N. Alqahtani, S. K. Porwal, E. D. James, D. M. Bis, J. A. Karty, A. L. Lane and R. Viswanathan, Org. Biomol. Chem., 2015, 13, 7177–7192,  10.1039/c5ob00537j.
165. X. Tang, J. Li, N. Millán-Aguiñaga, J. J. Zhang, E. C. O'Neill, J. A. Ugalde, P. R. Jensen, S. M. Mantovani and B. S. Moore, ACS Chem. Biol., 2015, 10, 2841–2849,  DOI:10.1021/acschembio.5b00658.
166. C. J. Schulze, W. M. Bray, M. H. Woerhmann, J. Stuart, R. S. Lokey and R. G. Linington, Chem. Biol., 2013, 20, 285–295,  DOI:10.1016/j.chembiol.2012.12.007.
167. J. L. Ochoa, W. M. Bray, R. S. Lokey and R. G. Linington, J. Nat. Prod., 2015, 78, 2242–2248,  DOI:10.1021/acs.jnatprod.5b00455.
168. H. Kim, I. Yang, S.-Y. Ryu, D. H. Won, A. G. Giri, W. Wang, H. Choi, J. Chin, D. Hahn, E. Kim, C. Han, J. Lee, S.-J. Nam, W.-K. Ho and H. Kang, J. Nat. Prod., 2015, 78, 363–367,  DOI:10.1021/np5007586.
169. X. Shi, W. Wei, W.-J. Zhang, C.-P. Hua, C.-J. Chen, H.-M. Ge, R.-X. Tan and R.-H. Jiao, J. Asian Nat. Prod. Res., 2015, 17, 143–148,  DOI:10.1080/10286020.2014.970536.
170. T. Yamada, T. Kikuchi and R. Tanaka, Tetrahedron Lett., 2015, 56, 1229–1232,  DOI:10.1016/j.tetlet.2015.01.066.
171. J. Wang, X. Wei, X. Qin, X. Lin, X. Zhou, S. Liao, B. Yang, J. Liu, Z. Tu and Y. Liu, Org. Lett., 2015, 17, 656–659,  DOI:10.1021/ol503646c.
172. J. Wang, Z. Wang, Z. Ju, J. Wan, S. Liao, X. Lin, T. Zhang, X. Zhou, H. Chen, Z. Tu and Y. Liu, Planta Med., 2015, 81, 160–166,  DOI:10.1055/s-0034-1383403.
173. Y. Hu, D. Dietrich, W. Xu, A. Patel, J. A. J. Thuss, J. Wang, W.-B. Yin, K. Qiao, K. N. Houk, J. C. Vederas and Y. Tang, Nat. Chem. Biol., 2014, 10, 552–554,  DOI:10.1038/nchembio.1527.
174. Y.-q. Tian, X.-p. Lin, J. Liu, K. Kaliyaperumal, W. Ai, Z.-r. Ju, B. Yang, J. Wang, X.-w. Yang and Y. Liu, Nat. Prod. Res., 2015, 29, 820–826,  DOI:10.1080/14786419.2014.988620.
175. S. Li, J. M. Finefield, J. D. Sunderhaus, T. J. McAfoos, R. M. Williams and D. H. Sherman, J. Am. Chem. Soc., 2012, 134, 788–791,  DOI:10.1021/ja2093212.
176. J. M. Finefield, J. C. Frisvad, D. H. Sherman and R. M. Williams, J. Nat. Prod., 2012, 75, 812–833,  DOI:10.1021/np200954v.
177. S. Tsukamoto, T. Kawabata, H. Kato, T. J. Greshock, H. Hirota, T. Ohta and R. M. Williams, Org. Lett., 2009, 11, 1297–1300,  DOI:10.1021/ol900071c.
178. J. D. Sunderhaus, T. J. McAfoos, J. M. Finefield, H. Kato, S. Y. Li, S. Tsukamoto, D. H. Sherman and R. M. Williams, Org. Lett., 2013, 15, 22–25,  DOI:10.1021/ol302901p.
179. H. Kato, T. Yoshida, T. Tokue, Y. Nojiri, H. Hirota, T. Ohta, R. M. Williams and S. Tsukamoto, Angew. Chem., Int. Ed., 2007, 46, 2254–2256,  DOI:10.1002/anie.200604381.
180. H. Kato, T. Nakahara, M. Yamaguchi, I. Kagiyama, J. M. Finefield, J. D. Sunderhaus, D. H. Sherman, R. M. Williams and S. Tsukamoto, Tetrahedron Lett., 2015, 56, 247–251,  DOI:10.1016/j.tetlet.2014.11.083.
181. R. Wang, Z. K. Guo, X. M. Li, Fu X. Chen, X. F. Zhan and M. H. Shen, Antonie van Leeuwenhoek, 2015, 108, 215–219,  DOI:10.1007/s10482-015-0462-y.
182. T. F. Solov'eva, B. P. Baskunov, O. V. Kiseleva and A. G. Kozlovskii, Mikrobiologiya, 1992, 61, 395–403.
183. P. He, S.-S. Tian, Y. Xu, H. Yu, Y.-N. Ji, H.-J. Zhu and J.-H. Li, Helv. Chim. Acta, 2015, 98, 819–822,  DOI:10.1002/hlca.201400329.
184. A. A. Yurchenko, O. F. Smetanina, A. I. Kalinovsky, N. N. Kirichuk, M. V. Pivkin, E. V. Ivanets, E. A. Yurchenko and S. S. Afiyatullov, Nat. Prod. Commun., 2015, 10, 1247–1297.
185. X. Ma, J. Peng, G. Wu, T. Zhu, G. Li, Q. Gu and D. Li, Tetrahedron, 2015, 71, 3522–3527,  DOI:10.1016/j.tet.2015.03.050.
186. J. Liu, X. Wei, E. L. Kim, X. Lin, X.-W. Yang, X. Zhou, B. Yang, J. H. Jung and Y. Liu, Tetrahedron, 2015, 71, 271–275,  DOI:10.1016/j.tet.2014.11.063.
187. P. Zhang, X.-M. Li, X. Li and B.-G. Wang, Phytochem. Lett., 2015, 12, 182–185,  DOI:10.1016/j.phytol.2015.03.017.
188. C. Prompanya, C. Fernandes, S. Cravo, M. M. M. Pinto, T. Dethoup, A. M. S. Silva and A. Kijjoa, Mar. Drugs, 2015, 13, 1432–1450,  DOI:10.3390/md13031432.
189. M. You, L. Liao, S. H. Hong, W. Park, D. I. Kwon, J. Lee, M. Noh, D.-C. Oh, K.-B. Oh and J. Shin, Mar. Drugs, 2015, 13, 1290–1303,  DOI:10.3390/md13031290.
190. X.-H. Nong, X.-Y. Zhang, X.-Y. Xu and S.-H. Qi, Nat. Prod. Commun., 2015, 10, 1033–1037.
191. M. Fredimoses, X. Zhou, W. Ai, X. Tian, B. Yang, X. Lin, J.-Y. Xian and Y. Liu, Nat. Prod. Res., 2015, 29, 158–162,  DOI:10.1080/14786419.2014.968154.
192. F. Cardoso-Martínez, J. M. de la Rosa, A. R. Díaz-Marrero, J. Darias, L. D'Croz, C. Cerella, M. Diederich and M. Cueto, Eur. J. Org. Chem., 2015, 2015, 2256–2261,  DOI:10.1002/ejoc.201403668.
193. L. Liao, M. You, B. Koo Chung, D.-C. Oh, K.-B. Oh and J. Shin, J. Nat. Prod., 2015, 78, 349–354,  DOI:10.1021/np500683u.
194. M. Zhou, J. Lou, Y.-K. Li, Y.-D. Wang, K. Zhou, B.-K. Ji, W. Dong, X.-M. Gao, G. Du and Q.-F. Hu, J. Braz. Chem. Soc., 2015, 26, 545–549,  DOI:10.5935/0103-5053.20150008.
195. C. Wang, C. Shao and M. Chen, CN 103351369 A 20131016, Faming Zhuanli Shenqing, 2013.
196. M. Chen, K.-L. Wang, M. Liu, Z.-G. She and C.-Y. Wang, Chem. Biodiversity, 2015, 12, 1398–1406,  DOI:10.1002/cbdv.201400321.
197. Y. Wang, S. Qi, Y. Zhan, N. Zhang, A.-a. Wu, F. Gui, K. Guo, Y. Yang, S. Cao, Z. Hu, Z. Zheng, S. Song, Q. Xu, Y. Shen and X. Deng, J. Nat. Prod., 2015, 78, 2405–2410,  DOI:10.1021/acs.jnatprod.5b00487.
198. F. Kong, C. Zhao, J. Hao, C. Wang, W. Wang, X. Huang and W. Zhu, RSC Adv., 2015, 5, 68852–68863,  10.1039/C5RA11185D.
199. P. Wang, S. Zhao, W. Ding, F. Qiu and J. Xu, Nat. Prod. Commun., 2015, 10, 1363–1367.
200. Y. Tian, X. Qin, X. Lin, K. Kaliyaperumal, X. Zhou, J. Liu, Z. Ju, Z. Tu and Y. Liu, J. Antibiot., 2015, 68, 703–706,  DOI:10.1038/ja.2015.55.
201. D.-C. Kim, T. H. Quang, N. T. T. Ngan, C.-S. Yoon, J. H. Sohn, J. H. Yim, Y. Feng, Y. Che, Y.-C. Kim and H. Oh, J. Nat. Prod., 2015, 78, 2948–2955,  DOI:10.1021/acs.jnatprod.5b00614.
202. J. F. Grove, J. Chem. Soc., Perkin Trans. 1, 1972, 2400–2406,  10.1039/p19720002400.
203. M. Nazir, H. Harms, I. Loef, S. Kehraus, F. El Maddah, I. Arslan, V. Rempel, C. Müller and G. König, Planta Med., 2015, 81, 1141–1145,  DOI:10.1055/s-0035-1545979.
204. L.-H. Meng, Y. Liu, X.-M. Li, G.-M. Xu, N.-Y. Ji and B.-G. Wang, J. Nat. Prod., 2015, 78, 2301–2305,  DOI:10.1021/acs.jnatprod.5b00450.
205. Z. Shang, L. Li, B. P. Espósito, A. A. Salim, Z. G. Khalil, M. Quezada, P. V. Bernhardt and R. J. Capon, Org. Biomol. Chem., 2015, 13, 7795–7802,  10.1039/c5ob01058f.
206. T. Nakada, M. Nakajima, H. Kobayashi, M. Takahashi and I. Tanaka, JP 2007153840 A 20070621, Jpn. Kokai Tokkyo Koho, 2007.
207. L. Du, A. J. Robles, J. B. King, D. R. Powell, A. N. Miller, S. L. Mooberry and R. H. Cichewicz, Angew. Chem., Int. Ed., 2014, 53, 804–809,  DOI:10.1002/anie.201306549.
208. X.-B. Li, L. Li, R.-X. Zhu, W. Li, W.-Q. Chang, L.-L. Zhang, X.-N. Wang, Z.-T. Zhao and H.-X. Lou, J. Nat. Prod., 2015, 78, 2155–2160,  DOI:10.1021/np501018w.
209. G.-H. Yu, G.-W. Wu, T.-J. Zhu, Q.-Q. Gu and D.-H. Li, J. Asian Nat. Prod. Res., 2015, 17, 120–124,  DOI:10.1080/10286020.2014.940330.
210. B. Gu, Y. Zhang, L. Ding, S. He, B. Wu, J. Dong, P. Zhu, J. Chen, J. Zhang and X. Yan, Mar. Drugs, 2015, 13, 354–365,  DOI:10.3390/md13010354.
211. F. Cao, Q. Yang, C.-L. Shao, C.-J. Kong, J.-J. Zheng, Y.-F. Liu and C.-Y. Wang, Mar. Drugs, 2015, 13, 4171–4178,  DOI:10.3390/md13074171.
212. M. Zhu, H. Gao, C. Wu, T. Zhu, Q. Che, Q. Gu, P. Guo and D. Li, Bioorg. Med. Chem. Lett., 2015, 25, 3606–3609,  DOI:10.1016/j.bmcl.2015.06.072.
213. D.-L. Zhao, C.-L. Shao, L.-S. Gan, M. Wang and C.-Y. Wang, J. Nat. Prod., 2015, 78, 286–293,  DOI:10.1021/np5009152.
214. K. R. Watts, J. Ratnam, K. H. Ang, K. Tenney, J. E. Compton, J. McKerrow and P. Crews, Bioorg. Med. Chem., 2010, 18, 2566–2574,  DOI:10.1016/j.bmc.2010.02.034.
215. M. Okamoto, K. Yoshida, I. Uchida, M. Nishikawa, M. Kohsaka and H. Aoki, Chem. Pharm. Bull., 1986, 34, 340–344,  DOI:10.1248/cpb.34.340.
216. H. Harms, B. Orlikova, S. Ji, D. Nesaei-Mosaferan, G. M. König and M. Diederich, Mar. Drugs, 2015, 13, 4949–4966,  DOI:10.3390/md13084949.
217. H. Harms, S. Kehraus, D. Nesaei-Mosaferan, P. Hufendieck, L. Meijer and G. M. König, Steroids, 2015, 104, 182–188,  DOI:10.1016/j.steroids.2015.09.012.
218. Q. Wu, C. Wu, H. Long, R. Chen, D. Liu, P. Proksch, P. Guo and W. Lin, J. Nat. Prod., 2015, 78, 2461–2470,  DOI:10.1021/acs.jnatprod.5b00578.
219. Q. Wu, H.-L. Long, D. Liu, P. Proksch and W.-H. Lin, J. Asian Nat. Prod. Res., 2015, 17, 1137–1145,  DOI:10.1080/10286020.2015.1119127.
220. X. Xia, J. Qi, Y. Liu, A. Jia, Y. Zhang, C. Liu, C. Gao and Z. She, Mar. Drugs, 2015, 13, 1124–1132,  DOI:10.3390/md13031124.
221. X. Chen, L. Si, D. Liu, P. Proksch, L. Zhang, D. Zhou and W. Lin, Eur. J. Med. Chem., 2015, 93, 182–195,  DOI:10.1016/j.ejmech.2015.02.006.
222. R. Marchelli, A. Dossena, A. Pochini and E. Dradi, J. Chem. Soc., Perkin Trans. 1, 1977, 713–717,  10.1039/p19770000713.
223. L.-N. Zhou, T.-J. Zhu, S.-X. Cai, Q.-Q. Gu and D.-H. Li, Helv. Chim. Acta, 2010, 93, 1758–1763,  DOI:10.1002/hlca.200900443.
224. J. Zhang, X.-P. Lin, L.-C. Li, B.-L. Zhong, X.-J. Liao, Y.-H. Liu and S.-H. Xu, RSC Adv., 2015, 5, 54645–54648,  10.1039/c5ra08559d.
225. T. Fukuda, M. Shinkai, E. Sasaki, K. Nagai, Y. Kurihara, A. Kanamoto and H. Tomoda, J. Antibiot., 2015, 68, 620–627,  DOI:10.1038/ja.2015.41.
226. T. Fukuda, K. Nagai, Y. Kurihara, A. Kanamoto and H. Tomoda, Nat. Prod. Sci., 2015, 21, 255–260,  DOI:10.20307/nps.2015.21.4.255.
227. L.-J. Ding, B.-B. Gu, W.-H. Jiao, W. Yuan, Y.-X. Li, W.-Z. Tang, H.-B. Yu, X.-J. Liao, B.-N. Han, Z.-Y. Li, S.-H. Xu and H.-W. Lin, Mar. Drugs, 2015, 13, 5579–5592,  DOI:10.3390/md13095579.
228. U. Zehavi and D. Ben-Ishai, J. Org. Chem., 1961, 26, 1097–1101,  DOI:10.1021/jo01063a029.
229. B. Kang, Z. Fu and S. H. Hong, J. Am. Chem. Soc., 2013, 135, 11704–11707,  DOI:10.1021/ja404695t.
230. L. Zhang, Y. Shen, F. Wang, Y. Leng and J.-K. Liu, Phytochemistry, 2009, 71, 100–103,  DOI:10.1016/j.phytochem.2009.09.020.
231. C.-J. Zheng, C.-L. Shao, M. Chen, Z.-G. Niu, D.-L. Zhao and C.-Y. Wang, Chem. Biodiversity, 2015, 12, 1407–1414,  DOI:10.1002/cbdv.201400331.
232. T. Gong, X. Zhen, B.-J. Li, J.-L. Yang and P. Zhu, J. Asian Nat. Prod. Res., 2015, 17, 633–637,  DOI:10.1080/10286020.2015.1040778.
233. A. Andolfi, A. Boari, M. Evidente, A. Cimmino, M. Vurro, G. Ash and A. Evidente, J. Nat. Prod., 2015, 78, 623–629,  DOI:10.1021/np500570h.
234. B. Wu, G. Chen, Z.-g. Liu and Y. Pei, Rec. Nat. Prod., 2015, 9, 271–275.
235. W. Zin, S. Buttachon, J. Buaruang, L. Gales, J. Pereira, M. Pinto, A. Silva and A. Kijjoa, Mar. Drugs, 2015, 13, 3776–3790,  DOI:10.3390/md13063776.
236. P. Zhang, X.-M. Li, J.-N. Wang, X. Li and B.-G. Wang, Phytochem. Lett., 2015, 11, 85–88,  DOI:10.1016/j.phytol.2014.11.014.
237. P. Zhang, X.-M. Li, J.-N. Wang and B.-G. Wang, Helv. Chim. Acta, 2015, 98, 800–804,  DOI:10.1002/hlca.201400328.
238. P. Zhang, X.-M. Li, J.-N. Wang, X. Li and B.-G. Wang, Chin. Chem. Lett., 2015, 26, 313–316,  DOI:10.1016/j.cclet.2014.11.020.
239. H. Wang, J. Hong, J. Yin, H. R. Moon, Y. Liu, X. Wei, D.-C. Oh and J. H. Jung, J. Nat. Prod., 2015, 78, 2832–2836,  DOI:10.1021/acs.jnatprod.5b00594.
240. Y. Liu, X.-M. Li, L.-H. Meng, W.-L. Jiang, G.-M. Xu, C.-G. Huang and B.-G. Wang, J. Nat. Prod., 2015, 78, 1294–1299,  DOI:10.1021/acs.jnatprod.5b00102.
241. X.-D. Li, X.-M. Li, G.-M. Xu, P. Zhang and B.-G. Wang, J. Nat. Prod., 2015, 78, 844–849,  DOI:10.1021/acs.jnatprod.5b00004.
242. L. Li, Y. Zhang, Z. Li, Z. Yu and T. Sun, J. Mex. Chem. Soc., 2015, 59, 53–58.
243. L. Chen, Q.-Q. Zhang, T. Zhou, Y.-Y. Zhao, M.-W. Gong, Q.-W. Xia, M.-G. Ying, Q.-H. Zheng and Q.-Y. Liu, Heterocycles, 2015, 91, 1007–1016,  DOI:10.3987/COM-15-13178.
244. Y. Liu, A. Mándi, X.-M. Li, L.-H. Meng, T. Kurtán and B.-G. Wang, Mar. Drugs, 2015, 13, 3640–3652,  DOI:10.3390/md13063640.
245. Q.-Y. Liu, T. Zhou, Y.-Y. Zhao, L. Chen, M.-W. Gong, Q.-W. Xia, M.-G. Ying, Q.-H. Zheng and Q.-Q. Zhang, Mar. Drugs, 2015, 13, 4733–4753,  DOI:10.3390/md13084733.
246. M. Makino, T. Endoh, Y. Ogawa, K. Watanabe and Y. Fujimoto, Heterocycles, 1998, 48, 1931–1934,  DOI:10.3987/COM-98-8253.
247. A. Mikami, T. Okazaki, N. Sakai, T. Ichihara, K. Hanada and K. Mizoue, J. Antibiot., 1996, 49, 985–989,  DOI:10.7164/antibiotics.49.985.
248. Sh. Sh. Afiyatullov, E. V. Leshchenko, M. P. Sobolevskaya, A. V. Gerasimenko, Yu. V. Khudyakova, N. N. Kirichuk and V. V. Mikhailov, Chem. Nat. Compd., 2015, 51, 111–115,  DOI:10.1007/s10600-015-1214-y.
249. X. Xu, X. Zhang, X. Nong, X. Wei and S. Qi, Tetrahedron, 2015, 71, 610–615,  DOI:10.1016/j.tet.2014.12.031.
250. M. Zhou, M.-M. Miao, G. Du, X.-N. Li, S.-Z. Shang, W. Zhao, Z.-H. Liu, G.-Y. Yang, C.-T. Che, Q.-F. Hu and X.-M. Gao, Org. Lett., 2014, 16, 5016–5019,  DOI:10.1021/ol502307u.
251. A. Numata, C. Takahashi, Y. Ito, T. Takada, K. Kawai, Y. Usami, E. Matsumura, M. Imachi, T. Ito and T. Hasegawa, Tetrahedron Lett., 1993, 34, 2355–2358,  DOI:10.1016/S0040-4039(00)77612-X.
252. H.-C. Lin, G. Chiou, Y.-H. Chooi, T. C. McMahon, W. Xu, N. K. Garg and Y. Tang, Angew. Chem., Int. Ed., 2015, 54, 3004–3007,  DOI:10.1002/anie.201411297.
253. Z. Ding, L. Zhang, J. Fu, Q. Che, D. Li, Q. Gu and T. Zhu, J. Antibiot., 2015, 68, 748–751,  DOI:10.1038/ja.2015.64.
254. D. Wang, Y.-R. Bao, X.-X. Yang, X.-S. Meng and G. Chen, Chem. Nat. Compd., 2015, 51, 733–735,  DOI:10.1007/s10600-015-1395-4.
255. Y.-Q. Fan, P.-H. Li, Y.-X. Chao, H. Chen, N. Du, Q.-X. He and K.-C. Liu, Mar. Drugs, 2015, 13, 6489–6504,  DOI:10.3390/md13106489.
256. B. Liu, H.-F. Wang, L.-H. Zhang, F. Liu, F.-J. He, J. Bai, H.-M. Hua, G. Chen and Y.-H. Pei, Nat. Prod. Res., 2015, 29, 2197–2202,  DOI:10.1080/14786419.2015.1008472.
257. X. Li, X.-M. Li, P. Zhang and B.-G. Wang, J. Asian Nat. Prod. Res., 2015, 17, 1204–1212,  DOI:10.1080/10286020.2015.1117454.
258. D.-L. Zhao, C.-L. Shao, Q. Zhang, K.-L. Wang, F.-F. Guan, T. Shi and C.-Y. Wang, J. Nat. Prod., 2015, 78, 2310–2314,  DOI:10.1021/acs.jnatprod.5b00575.
259. CAS Registry Number: 1083195-01-0, Aurora Screening Library, SciFinder database, September 2016.
260. M.-W. Xia, C.-B. Cui, C.-W. Li, C.-J. Wu, J.-X. Peng and D.-H. Li, Mar. Drugs, 2015, 13, 5219–5236,  DOI:10.3390/md13085219.
261. S. S. Afiyatullov, E. V. Leshchenko, M. P. Sobolevskaya, V. A. Denisenko, N. N. Kirichuk, Y. V. Khudyakova, T. P. T. Hoai, P. S. Dmitrenok, E. S. Menchinskaya, E. A. Pislyagin and D. V. Berdyshev, Phytochem. Lett., 2015, 14, 209–214,  DOI:10.1016/j.phytol.2015.10.011.
262. H. Yamazaki, W. Nakayama, O. Takahashi, R. Kirikoshi, Y. Izumikawa, K. Iwasaki, K. Toraiwa, K. Ukai, H. Rotinsulu, D. S. Wewengkang, D. A. Sumilat, R. E. P. Mangindaan and M. Namikoshi, Bioorg. Med. Chem. Lett., 2015, 25, 3087–3090,  DOI:10.1016/j.bmcl.2015.06.026.
263. L. A. Shaala and D. T. A. Youssef, Mar. Drugs, 2015, 13, 1698–1709,  DOI:10.3390/md13041698.
264. F. Cardoso-Martínez, J. M. de la Rosa, A. R. Díaz-Marrero, J. Darias, C. Cerella, M. Diederich and M. Cueto, Org. Biomol. Chem., 2015, 13, 7248–7256,  10.1039/C5OB00773A.
265. J. W. Kim, S.-K. Ko, S. Son, K.-S. Shin, I.-J. Ryoo, Y.-S. Hong, H. Oh, B. Y. Hwang, H. Hirota, S. Takahashi, B. Y. Kim, H. Osada, J.-H. Jang and J. S. Ahn, Bioorg. Med. Chem. Lett., 2015, 25, 5398–5401,  DOI:10.1016/j.bmcl.2015.09.026.
266. W. Guo, Z. Zhang, T. Zhu, Q. Gu and D. Li, J. Nat. Prod., 2015, 78, 2699–2703,  DOI:10.1021/acs.jnatprod.5b00655.
267. C. Lee, J. H. Sohn, J.-H. Jang, J. S. Ahn, H. Oh, J. Baltrusaitis, In H. Hwang and J. B. Gloer, J. Antibiot., 2015, 68, 715–718,  DOI:10.1038/ja.2015.56.
268. S. M. Kim, S. Son, J. W. Kim, E. S. Jeon, S.-K. Ko, I.-J. Ryoo, K.-S. Shin, H. Hirota, S. Takahashi, H. Osada, J.-H. Jang and J. S. Ahn, Nat. Prod. Sci., 2015, 21, 231–236,  DOI:10.20307/nps.2015.21.4.231.
269. I. A. M. Asiri, J. M. Badr and D. T. A. Youssef, Phytochem. Lett., 2015, 13, 53–58,  DOI:10.1016/j.phytol.2015.05.014.
270. J. Santesson, Acta Chem. Scand., 1968, 22, 1698–1699,  DOI:10.3891/acta.chem.scand.22-1698.
271. W. B. Turner and B. C. Aldridge, J. Chem. Soc. C, 1970, 2598–2600.
272. H. Chen, N. Aktas, B. Konuklugil, A. Mándi, G. Daletos, W. Lin, H. Dai, T. Kurtán and P. Proksch, Tetrahedron Lett., 2015, 56, 5317–5320,  DOI:10.1016/j.tetlet.2015.07.072.
273. Y.-L. Jia, M.-Y. Wei, H.-Y. Chen, F.-F. Guan, C.-Y. Wang and C.-L. Shao, Org. Lett., 2015, 17, 4216–4219,  DOI:10.1021/acs.orglett.5b01995.
274. J. Arunpanichlert, V. Rukachaisirikul, S. Phongpaichit, O. Supaphon and J. Sakayaroj, Tetrahedron, 2015, 71, 882–888,  DOI:10.1016/j.tet.2014.12.009.
275. Y.-L. Jia, F.-F. Guan, J. Ma, C.-Y. Wang and C.-L. Shao, Nat. Prod. Sci., 2015, 21, 227–230,  DOI:10.20307/nps.2015.21.4.227.
276. N. J. Cusack, B. J. Hildick, D. H. Robinson, P. W. Rugg and G. Shaw, J. Chem. Soc., Perkin Trans. 1, 1973, 1720–1731,  10.1039/p19730001720.
277. Q. Xing, D. Li, Z.-Y. Guo, C.-Y. Wang and C.-L. Shao, Chem. Nat. Compd., 2015, 51, 1080–1084,  DOI:10.1007/s10600-015-1497-z.
278. E. Li, L. Jiang, L. Guo, H. Zhang and Y. Che, Bioorg. Med. Chem., 2008, 16, 7894–7899,  DOI:10.1016/j.bmc.2008.07.075.
279. M. Y. Wei, D. Li, C. L. Shao, D. S. Deng and C. Y. Wang, Mar. Drugs, 2013, 11, 1050–1060,  DOI:10.3390/md11041050.
280. M. F. Elsebai, F. E. Maddah, S. Kehraus and G. M. König, Nat. Prod. Commun., 2015, 10, 637–646.
281. S. W. Tanenbaum, B. H. Patwardhan, L. Haynes and M. Flashner, Life Sci., 1982, 30, 1927–1931,  DOI:10.1016/0024-3205(82)90474-X.
282. E. L. Kim, H. Wang, J. H. Park, J. Hong, J. S. Choi, D. S. Im, H. Y. Chung and J. H. Jung, Bioorg. Med. Chem. Lett., 2015, 25, 2096–2099,  DOI:10.1016/j.bmcl.2015.03.080.
283. C. J. Chen, Y. Q. Zhou, X. X. Liu, W. J. Zhang, S. S. Hu, Li P. Lin, G. M. Huo, R. H. Jiao, R. X. Tan and H. M. Ge, Tetrahedron Lett., 2015, 56, 6183–6189,  DOI:10.1016/j.tetlet.2015.09.079.
284. D.-F. Yan, W.-J. Lan, K.-T. Wang, L. Huang, C.-W. Jiang and H.-J. Li, Nat. Prod. Commun., 2015, 10, 621–623.
285. W. Liu, H.-J. Li, M.-Y. Xu, Y.-C. Ju, L.-Y. Wang, J. Xu, D.-P. Yang and W.-J. Lan, Org. Lett., 2015, 17, 5156–5159,  DOI:10.1021/acs.orglett.5b02311.
286. L. Figueroa, C. Jiménez, J. Rodríguez, C. Areche, R. Chávez, M. Henríquez, M. de la Cruz, C. Díaz, Y. Segade and I. Vaca, J. Nat. Prod., 2015, 78, 919–923,  DOI:10.1021/np500906k.
287. E. L. F. Ferreira, D. E. Williams, L. P. Ióca, R. P. Morais-Urano, M. F. C. Santos, B. O. Patrick, L. M. Elias, S. P. Lira, A. G. Ferreira, M. R. Z. Passarini, L. D. Sette, R. J. Andersen and R. G. S. Berlinck, Org. Lett., 2015, 17, 5152–5155,  DOI:10.1021/acs.orglett.5b02060.
288. J. Hargreaves, J.-O. Park, E. L. Ghisalberti, K. Sivasithamparam, B. W. Skelton and A. H. White, Aust. J. Chem., 2002, 55, 625–627,  DOI:10.1071/ch02154.
289. B.-F. Yan, S.-T. Fang, W.-Z. Li, S.-J. Liu, J.-H. Wang and C.-H. Xia, Nat. Prod. Res., 2015, 29, 2013–2017,  DOI:10.1080/14786419.2015.1027890.
290. Z. Lin, X. Ma, H. Wei, D. Li, Q. Gu and T. Zhu, RSC Adv., 2015, 5, 35262–35266,  10.1039/c5ra01923k.
291. S. Niu, D. Liu, P. Proksch, Z. Shao and W. Lin, Mar. Drugs, 2015, 13, 2526–2540,  DOI:10.3390/md13042526.
292. X. Ma, H. Wang, F. Li, T. Zhu, Q. Gu and D. Li, Tetrahedron Lett., 2015, 56, 7053–7055,  DOI:10.1016/j.tetlet.2015.11.029.
293. C. Qin, X. Lin, X. Lu, J. Wan, X. Zhou, S. Liao, Z. Tu, S. Xu and Y. Liu, J. Antibiot., 2015, 68, 121–125,  DOI:10.1038/ja.2014.97.
294. S. Ngokpol, W. Suwakulsiri, S. Sureram, K. Lirdprapamongkol, T. Aree, S. Wiyakrutta, C. Mahidol, S. Ruchirawat and P. Kittakoop, Mar. Drugs, 2015, 13, 3567–3580,  DOI:10.3390/md13063567.
295. H. Oh, T. O. Kwon, J. B. Gloer, L. Marvanova and C. A. Shearer, J. Nat. Prod., 1999, 62, 580–583,  DOI:10.1021/np980496m.
296. M. Chen, L. Han, C.-L. Shao, Z.-G. She and C.-Y. Wang, Chem. Biodiversity, 2015, 12, 443–450,  DOI:10.1002/cbdv.201400267.
297. B. Wu, B. Ohlendorf, V. Oesker, J. Wiese, S. Malien, R. Schmaljohann and J. F. Imhoff, Mar. Biotechnol., 2015, 17, 110–119,  DOI:10.1007/s10126-014-9599-3.
298. Y.-L. Sun, J. Wang, Y.-F. Wang, X.-Y. Zhang, X.-H. Nong, M.-Y. Chen, X.-Y. Xu and S.-H. Qi, Tetrahedron, 2015, 71, 9328–9332,  DOI:10.1016/j.tet.2015.10.010.
299. R. D. Stipanovic and C. R. Howell, J. Antibiot., 1982, 35, 1326–1330,  DOI:10.7164/antibiotics.35.1326.
300. P. Seephonkai, P. Kongsaeree, S. Prabpai, M. Isaka and Y. Thebtaranonth, Org. Lett., 2006, 8, 3073–3075,  DOI:10.1021/ol061046l.
301. E. Garo, C. M. Starks, P. R. Jensen, W. Fenical, E. Lobkovsky and J. Clardy, J. Nat. Prod., 2003, 66, 423–426,  DOI:10.1021/np0204390.
302. H. Nakano, M. Hara, T. Mejiro, K. Ando, Y. Saito and M. Morimoto, JP 02218686 A 19900831, Jpn. Kokai Tokkyo Koho, 1990.
303. H. Yamazaki, H. Rotinsulu, R. Narita, R. Takahashi and M. Namikoshi, J. Nat. Prod., 2015, 78, 2319–2321,  DOI:10.1021/acs.jnatprod.5b00669.
304. H. Yamazaki, O. Takahashi, K. Murakami and M. Namikoshi, Tetrahedron Lett., 2015, 56, 6262–6265,  DOI:10.1016/j.tetlet.2015.09.113.
305. T. Yamada, Y. Umebayashi, M. Kawashima, Y. Sugiura, T. Kikuchi and R. Tanaka, Mar. Drugs, 2015, 13, 3231–3240,  DOI:10.3390/md13053231.
306. B. Li, Q.-X. Huang, D. Gao, D. Liu, Y.-B. Ji, H.-G. Liu and W.-H. Lin, J. Asian Nat. Prod. Res., 2015, 17, 468–474,  DOI:10.1080/10286020.2015.1042371.
307. H. Yamazaki, R. Saito, O. Takahashi, R. Kirikoshi, K. Toraiwa, K. Iwasaki, Y. Izumikawa, W. Nakayama and M. Namikoshi, J. Antibiot., 2015, 68, 628–632,  DOI:10.1038/ja.2015.44.
308. Y. Zhao, L. Si, D. Liu, P. Proksch, D. Zhou and W. Lin, Tetrahedron, 2015, 71, 2708–2718,  DOI:10.1016/j.tet.2015.03.033.
309. J. G. Ondeyka, S. K. Smith, D. L. Zink, F. Vicente, A. Basilio, G. F. Bills, J. D. Polishook, C. Garlisi, D. Mcguinness, E. Smith, H. Qiu, C. J. Gill, R. G. K. Donald, J. W. Phillips, M. A. Goetz and S. B. Singh, J. Antibiot., 2014, 67, 527–531,  DOI:10.1038/ja.2014.33.
310. B. Wu, J. Wiese, A. Labes, A. Kramer, R. Schmaljohann and J. F. Imhoff, Mar. Drugs, 2015, 13, 4617–4632,  DOI:10.3390/md13084617.
311. S. F. Seibert, A. Krick, E. Eguereva and S. Kehraus, Org. Lett., 2007, 9, 239–242,  DOI:10.1021/ol0626802.
312. S. Chang, S. Hur and R. Britton, Angew. Chem., Int. Ed., 2015, 54, 211–214,  DOI:10.1002/anie.201408905.
313. S. Chang, S. Hur and R. Britton, Chem.–Eur. J., 2015, 21, 16646–16653,  DOI:10.1002/chem.201502754.
314. F. Kong and G. T. Carter, Tetrahedron Lett., 2003, 44, 3119–3122,  DOI:10.1016/S0040-4039(03)00518-5.
315. E. C. Sherer, J. R. Cheeseman and R. Thomas Williamson, Org. Biomol. Chem., 2015, 13, 4169–4173,  10.1039/c5ob00082c.
316. Y. Sun, L. Tian, J. Huang, H.-Y. Ma, Z. Zheng, A.-L. Lv, K. Yasukawa and Y.-H. Pei, Org. Lett., 2008, 10, 393–396,  DOI:10.1021/ol702674f.
317. H. Shigehisa, H. Kikuchi, T. Suzuki and K. Hiroya, Eur. J. Org. Chem., 2015, 2015, 7670–7673,  DOI:10.1002/ejoc.201501281.
318. K. Kai, H. Yoshikawa, Y.-H. Kuo, K. Akiyama and H. Hayashi, Biosci., Biotechnol., Biochem., 2010, 74, 1309–1311,  DOI:10.1271/bbb.100098.
319. Y. Masuda, R. Tanaka, A. Ganesan and T. Doi, J. Nat. Prod., 2015, 78, 2286–2291,  DOI:10.1021/acs.jnatprod.5b00643.
320. D. Kurnia, K. Akiyama and H. Hayashi, Phytochemistry, 2007, 68, 697–702,  DOI:10.1016/j.phytochem.2006.11.023.
321. A. C. D. S. Dias, N. Ruiz, A. Couzinet-Mossion, S. Bertrand, M. Duflos, Y.-F. Pouchus, G. Barnathan, H. Nazih and G. Wielgosz-Collin, Mar. Drugs, 2015, 13, 4934–4948,  DOI:10.3390/md13084934.
322. B. S. F. Rodrigues, B. D. B. Sahm, P. C. Jimenez, F. C. L. Pinto, J. Mafezoli, M. C. Mattos, E. Rodrigues-Filho, L. H. Pfenning, L. M. Abreu, L. V. Costa-Lotufo and M. C. F. Oliveira, Chem. Biodiversity, 2015, 12, 432–442,  DOI:10.1002/cbdv.201400193.
323. CAS Registry Number: 913690-77-4, K05.567.876, Aurora Screening Library, Aurora Fine Chemicals LLC, 7 Apr 2016.
324. Y.-Y. Bu, H. Yamazaki, K. Ukai and M. Namikoshi, J. Antibiot., 2015, 68, 537–539,  DOI:10.1038/ja.2015.21.
325. A. H. Aly, R. Edrada-Ebel, I. D. Indriani, V. Wray, W. E. G. Mueller, F. Totzke, U. Zirrgiebel, C. Schaechtele, M. H. G. Kubbutat, W. H. Lin, P. Proksch and R. Ebel, J. Nat. Prod., 2008, 71, 972–980,  DOI:10.1021/np070447m.
326. U. W. Hawas, S. El-Desouky, L. Abou El-Kassem and W. Elkhateeb, Appl. Biochem. Microbiol., 2015, 51, 579–584,  DOI:10.1134/s0003683815050099.
327. F.-P. Miao, X.-R. Liang, X.-H. Liu and N.-Y. Ji, J. Nat. Prod., 2014, 77, 429–432,  DOI:10.1021/np401047w.
328. Y. Liu, S. C. Virgil, R. H. Grubbs and B. M. Stoltz, Angew. Chem., Int. Ed., 2015, 54, 11800–11803,  DOI:10.1002/anie.201505161.
329. S. Tsukamoto, H. Kato, M. Samizo, Y. Nojiri, H. Onuki, H. Hirota and T. Ohta, J. Nat. Prod., 2008, 71, 2064–2067,  DOI:10.1021/np800471y.
330. E. V. Mercado-Marin, P. Garcia-Reynaga, S. Romminger, E. F. Pimenta, D. K. Romney, M. W. Lodewyk, D. E. Williams, R. J. Andersen, S. J. Miller, D. J. Tantillo, R. G. S. Berlinck and R. Sarpong, Nature, 2014, 509, 318–324,  DOI:10.1038/nature13273.
331. E. V. Mercado-Marin and R. Sarpong, Chem. Sci., 2015, 6, 5048–5052,  10.1039/c5sc01977j.
332. R. Jadulco, G. Brauers, R. A. Edrada, R. Ebel and V. Wray, J. Nat. Prod., 2002, 65, 730–733,  DOI:10.1021/np010390i.
333. J. Heimberger, H. C. Cade, J. Padgett, V. Sittaramane and A. Shaikh, Bioorg. Med. Chem. Lett., 2015, 25, 1192–1195,  DOI:10.1016/j.bmcl.2015.01.065.
334. C. L. Shao, H. X. Wu, C. Y. Wang, Q. A. Liu, Y. Xu, M. Y. Wei, P. Y. Qian, Y. C. Gu, C. J. Zheng, Z. G. She and Y. C. Lin, J. Nat. Prod., 2011, 74, 629–633,  DOI:10.1021/np100641b.
335. C. L. Shao, H. X. Wu, C. Y. Wang, Q. A. Liu, Y. Xu, M. Y. Wei, P. Y. Qian, Y. C. Gu, C. J. Zheng, Z. G. She and Y. C. Lin, J. Nat. Prod., 2013, 76, 302,  DOI:10.1021/np400079t.
336. B. Mahankali and P. Srihari, Eur. J. Org. Chem., 2015, 2015, 3983–3993,  DOI:10.1002/ejoc.201500395.
337. P. Sun, D. X. Xu, A. Mandl, T. Kurtan, T. J. Li, B. Schulz and W. Zhang, J. Org. Chem., 2013, 78, 7030–7047,  DOI:10.1021/jo400861j.
338. D. K. Mohapatra, K. Pulluri, S. Gajula and J. S. Yadav, Tetrahedron Lett., 2015, 56, 6377–6380,  DOI:10.1016/j.tetlet.2015.09.126.
339. D. K. Mohapatra, D. Prabhakar Reddy, S. Gajula, K. Pulluri and J. S. Yadav, Asian J. Org. Chem., 2015, 4, 452–461,  DOI:10.1002/ajoc.201500037.
340. F. Z. Wang, Z. Huang, X. F. Shi, Y. C. Chen, W. M. Zhang, X. P. Tian, J. Li and S. Zhang, Bioorg. Med. Chem. Lett., 2012, 22, 7265–7267,  DOI:10.1016/j.bmcl.2012.08.115.
341. T. C. Adams, J. N. Payette, J. H. Cheah and M. Movassaghi, Org. Lett., 2015, 17, 4268–4271,  DOI:10.1021/acs.orglett.5b02059.
342. H. Tomoda, H. Nishida, R. Masuma, J. Cao, S. Okuda and S. Omura, J. Antibiot., 1991, 44, 136–143,  DOI:10.7164/antibiotics.44.136.
343. K. Suzuki, K. Nozawa, S. Udagawa, S. Nakajima and K. Kawai, Phytochemistry, 1991, 30, 2096–2098,  DOI:10.1016/0031-9422(91)85080-J.
344. D. B. Sauer, L. M. Seitz, R. Burroughs, H. E. Mohr, J. L. West, R. J. Milleret and H. D. Anthony, J. Agric. Food Chem., 1978, 26, 1380–1383,  DOI:10.1021/jf60220a022.
345. S. S. Gao, X. M. Li and B. G. Wang, Nat. Prod. Commun., 2009, 4, 1477–1480.
346. C.-J. Zheng, X.-M. Fu, X.-L. Zhang, W.-W. Kong and C.-Y. Wang, Chem. Nat. Compd., 2015, 51, 766–768,  DOI:10.1007/s10600-015-1406-5.
347. G. R. Pettit, Experientia, 1973, 29, 521–523,  DOI:10.1007/bf01926639.
348. F. J. Schmitz, D. J. Vanderah, K. H. Hollenbeak, C. E. L. Enwall, Y. Gopichand, P. K. SenGupta and M. B. Hossain, J. Org. Chem., 1983, 48, 3941–3945,  DOI:10.1021/jo00170a011.
349. R.-M. Huang, W. Ma, J.-D. Dong, X.-F. Zhou, T. Xu, K. J. Lee, X. Yang, S.-H. Xu and Y. Liu, Molecules, 2010, 15, 871–877,  DOI:10.3390/molecules15020871.
350. C. Brack, A. Mikolasch and F. Schauer, Mar. Biotechnol., 2014, 16, 385–395,  DOI:10.1007/s10126-014-9559-y.
351. C. Gao, L. Lin, B. Long, Y. Chen, B. He, H. Sun and R. Huang, Nat. Prod. Res., 2014, 28, 473–476,  DOI:10.1080/14786419.2013.879134.
352. X. Chen, Y. Mou, J. Ling, N. Wang, X. Wang and J. Hu, World J. Microbiol. Biotechnol., 2015, 31, 247–253,  DOI:10.1007/s11274-014-1759-0.
353. L. J. Fremlin, A. M. Piggott, E. Lacey and R. J. Capon, J. Nat. Prod., 2009, 72, 666–670,  DOI:10.1021/np800777f.
354. W. Ko, J. Hak Sohn, Y.-C. Kim and H. Oh, Nat. Prod. Sci., 2015, 21, 240–247,  DOI:10.20307/nps.2015.21.4.240.
355. S. Niu, D. Liu, X. Hu, P. Proksch, Z. Shao and W. Lin, J. Nat. Prod., 2014, 77, 1021–1030,  DOI:10.1021/np5000457.
356. C. Wu, R. Chen, M. Liu, D. Liu, X. Li, S. Wang, S. Niu, P. Guo and W. Lin, Mar. Drugs, 2015, 13, 6352–6365,  DOI:10.3390/md13106352.
357. Q. Zhang, B. Bao, L. Ni, L. Chen, X. Tian, L. Ge and W. Wu, Zhongguo Shenghua Yaowu Zazhi, 2012, 33, 515–518.
358. G. Wang, W. Wu, Q. Zhu, S. Fu, X. Wang, S. Hong, R. Guo and B. Bao, Chin. J. Chem., 2015, 33, 1089–1095,  DOI:10.1002/cjoc.201500176.
359. T. Yan, W. Wu, T. Su, J. Chen, Q. Zhu, C. Zhang, X. Wang and B. Bao, Arch. Pharmacal Res., 2015, 38, 1530–1540,  DOI:10.1007/s12272-014-0518-y.
360. Z. Yu, G. Lang, I. Kajahn, R. Schmaljohann and J. F. Imhoff, J. Nat. Prod., 2008, 71, 1052–1054,  DOI:10.1021/np070580e.
361. A. Kramer, H. C. Beck, A. Kumar, L. P. Kristensen, J. F. Imhoff and A. Labes, PLoS One, 2015, 10, e0140047,  DOI:10.1371/journal.pone.0140047.
362. M. Lukassen, W. Saei, T. Sondergaard, A. Tamminen, A. Kumar, F. Kempken, M. Wiebe and J. Sørensen, Mar. Drugs, 2015, 13, 4331–4343,  DOI:10.3390/md13074331.
363. A. Kumar, B. Henrissat, M. Arvas, M. F. Syed, N. Thieme, J. Philipp Benz, J. L. Sørensen, E. Record, S. Pöggeler and F. Kempken, PLoS One, 2015, 10, e0140398,  DOI:10.1371/journal.pone.0140398, 26505484.
364. J. Wang, W. Ding, R. Wang, Y. Du, H. Liu, X. Kong and C. Li, Mar. Drugs, 2015, 13, 4492–4504,  DOI:10.3390/md13074492.
365. Z.-Q. Bai, X. Lin, J. Wang, X. Zhou, J. Liu, B. Yang, X. Yang, S. Liao, L. Wang and Y. Liu, Mar. Drugs, 2015, 13, 237–248,  DOI:10.3390/md13010237.
366. Y. Liu, X.-M. Li, L.-H. Meng and B.-G. Wang, Phytochem. Lett., 2015, 12, 232–236,  DOI:10.1016/j.phytol.2015.04.009.
367. S. Cai, S. Sun, J. Peng, X. Kong, H. Zhou, T. Zhu, Q. Gu and D. Li, Tetrahedron, 2015, 71, 3715–3719,  DOI:10.1016/j.tet.2014.09.019.
368. P. Liu, C. Wang, Z. Lu, T. Zhu, K. Hong and W. Zhu, Nat. Prod. Commun., 2015, 10, 2123–2129.
369. G. Wu, G. Yu, T. Kurtán, A. Mándi, J. Peng, X. Mo, M. Liu, H. Li, X. Sun, J. Li, T. Zhu, Q. Gu and D. Li, J. Nat. Prod., 2015, 78, 2691–2698,  DOI:10.1021/acs.jnatprod.5b00636.
370. Z. Xiao, S. Lin, C. Tan, Y. Lu, L. He, X. Huang and Z. She, Mar. Drugs, 2015, 13, 366–378,  DOI:10.3390/md13010366.
371. C.-J. Zheng, L.-Y. Wu, X.-B. Li, X.-M. Song, Z.-G. Niu, X.-P. Song, G.-Y. Chen and C.-Y. Wang, Helv. Chim. Acta, 2015, 98, 368–373,  DOI:10.1002/hlca.201400197.
372. G. Ding, S. Liu, L. Guo, Y. Zhou and Y. Che, J. Nat. Prod., 2008, 71, 615–618,  DOI:10.1021/np070590f.
373. Y. Liu, S. Chen, Z. Liu, Y. Lu, G. Xia, H. Liu, L. He and Z. She, Mar. Drugs, 2015, 13, 3091–3102,  DOI:10.3390/md13053091.
374. Y. Lin, L. Wang, Y. Wang, W. Wang, J. Hao and W. Zhu, Chin. J. Org. Chem., 2015, 35, 1955–1960,  DOI:10.6023/cjoc201504007.
375. Z. Ju, X. Lin, X. Lu, Z. Tu, J. Wang, K. Kaliyaperumal, J. Liu, Y. Tian, S. Xu and Y. Liu, J. Antibiot., 2015, 68, 653–656,  DOI:10.1038/ja.2015.46.
376. W. Ai, X. Lin, Z. Wang, X. Lu, F. Mangaladoss, X. Yang, X. Zhou, Z. Tu and Y. Liu, J. Antibiot., 2015, 68, 213–215,  DOI:10.1038/ja.2014.126.
377. W. Kongyen, V. Rukachaisirikul, S. Phongpaichit and J. Sakayaroj, Nat. Prod. Res., 2015, 29, 1995–1999,  DOI:10.1080/14786419.2015.1022542.
378. L.-H. Meng, F.-Y. Du, X.-M. Li, P. Pedpradab, G.-M. Xu and B. G. Wang, J. Nat. Prod., 2015, 78, 909–913,  DOI:10.1021/np5007839.
379. S. V. Sharma, C. Oneyama, H. Nakano, T. Agatsuma, Y. Kanda, N. Tsumagari and K. Ando, WO 2003006060 A1 20030123, PCT Int. Appl., 2003.
380. S. Qi, Y. Wang, Z. Zheng, Q. Xu and X. Deng, Nat. Prod. Commun., 2015, 10, 2027–2030.
381. Y. Tezuka, Q. Huang, T. Kikuchi, A. Nishi and K. Tubaki, Chem. Pharm. Bull., 1994, 42, 2612–2617,  DOI:10.1248/cpb.42.2612.
382. Y. Shiono, F. Shibuya, T. Koseki, Harizon, U. Supratman, S. Uesugi and K.-i. Kimura, J. Asian Nat. Prod. Res., 2015, 17, 403–408,  DOI:10.1080/10286020.2014.961919.
383. F. Lv, G. Daletos, W. Lin and P. Proksch, Nat. Prod. Commun., 2015, 10, 1667–1670.
384. C. Intaraudom, S. Nitthithanasilp, P. Rachtawee, T. Boonruangprapa, S. Prabpai, P. Kongsaeree and P. Pittayakhajonwut, Phytochemistry, 2015, 120, 19–27,  DOI:10.1016/j.phytochem.2015.11.003.
385. S. Chen, Z. Liu, Y. Liu, Y. Lu, L. He and Z. She, Beilstein J. Org. Chem., 2015, 11, 1187–1193,  DOI:10.3762/bjoc.11.133.
386. Q.-H. Zhang, L. Tian, Z.-L. Sun, S. Fang, G.-L. Cai, Y.-J. Wang and Y.-H. Pei, J. Asian Nat. Prod. Res., 2015, 17, 497–503,  DOI:10.1080/10286020.2015.1009899.
387. M. Isaka, P. Chinthanom, P. Rachtawee, K. Srichomthong, P. Srikitikulchai, P. Kongsaeree and S. Prabpai, J. Antibiot., 2015, 68, 334–338,  DOI:10.1038/ja.2014.153.
388. Y. Ma, J. Li, M. Huang, L. Liu, J. Wang and Y. Lin, Mar. Drugs, 2015, 13, 6306–6318,  DOI:10.3390/md13106306.
389. L.-H. Meng, P. Zhang, X.-M. Li and B.-G. Wang, Mar. Drugs, 2015, 13, 276–287,  DOI:10.3390/md13010276.
390. L.-H. Meng, X.-M. Li, Y. Liu and B.-G. Wang, Chin. Chem. Lett., 2015, 26, 610–612,  DOI:10.1016/j.cclet.2015.01.024.
391. K. Tatsuta, A. Furuyama, T. Yano, Y. Suzuki, T. Ogura and S. Hosokawa, Tetrahedron Lett., 2008, 49, 4036–4039,  DOI:10.1016/j.tetlet.2008.04.074.
392. C. Darsih, V. Prachyawarakorn, S. Wiyakrutta, C. Mahidol, S. Ruchirawat and P. Kittakoop, RSC Adv., 2015, 5, 70595–70603,  10.1039/c5ra13735g.
393. W. Guo, D. Li, J. Peng, T. Zhu, Q. Gu and D. Li, J. Nat. Prod., 2015, 78, 306–310,  DOI:10.1021/np500586r.
394. Y.-Z. Wu, F. Qiao, G.-W. Xu, J. Zhao, J.-F. Teng, C. Li and W.-J. Deng, Phytochem. Lett., 2015, 12, 148–152,  DOI:10.1016/j.phytol.2015.03.007.
395. J. Liu, M. Xu, M.-y. Zhu and Y. Feng, Nat. Prod. Commun., 2015, 10, 1203–1208.
396. P. Zhang, X.-M. Li, H. Liu, X. Li and B.-G. Wang, Phytochem. Lett., 2015, 13, 160–164,  DOI:10.1016/j.phytol.2015.06.009.
397. W. Guo, X. Kong, T. Zhu, Q. Gu and D. Li, Arch. Pharmacal Res., 2015, 38, 1449–1454,  DOI:10.1007/s12272-014-0513-3.
398. N. Ohi, B. Aoki, K. Moro, T. Kuroki, N. Sugimura, T. Noto, T. Nehashi, M. Matsumoto, H. Okazaki and I. Matsunaga, J. Antibiot., 1986, 39, 242–250,  DOI:10.7164/antibiotics.39.242.
399. Y. Liu, Q. Yang, G. Xia, H. Huang, H. Li, L. Ma, Y. Lu, L. He, X. Xia and Z. She, J. Nat. Prod., 2015, 78, 1816–1822,  DOI:10.1021/np500885f.
400. J. Li, Y.-s. Zhong, J. Yuan, X. Zhu, Y.-j. Lu, Y.-c. Lin and L. Liu, Nat. Prod. Commun., 2015, 10, 1549–1600.
401. J. Wang, X. Wei, X. Qin, H. Chen, X. Lin, T. Zhang, X. Yang, S. Liao, B. Yang, J. Liu, X. Zhou, Z. Tu and Y. Liu, Phytochem. Lett., 2015, 12, 59–62,  DOI:10.1016/j.phytol.2015.02.013.
402. K. Mori and K. Uenishi, Liebigs Ann., 1996, 1–6.
403. X. Song, X. Zhou, X. Li, C. Zheng, G. Huang, Z. Yu, X. Song and G. Chen, Chin. J. Org. Chem., 2015, 35, 2102–2107,  DOI:10.6023/cjoc201505044.
404. T. Jiang, L. Tian, A. Guo, H. Fu, Y. Pei and W. Lin, Yaoxue Xuebao, 2002, 37, 271–274.
405. N. K. Bose and D. N. Chaudhury, J. Indian Chem. Soc., 1966, 43, 411–415.
406. T. El-Elimat, M. Figueroa, H. A. Raja, T. N. Graf, S. M. Swanson, J. O. Falkinham, M. C. Wani, C. J. Pearce and N. H. Oberlies, Eur. J. Org. Chem., 2015, 2015, 109–121,  DOI:10.1002/ejoc.201402984.
407. X.-M. Zhou, C.-J. Zheng, G.-Y. Chen, X.-P. Song, C.-R. Han, X.-Z. Tang, R.-J. Liu and L.-L. Ren, J. Antibiot., 2015, 68, 501–503,  DOI:10.1038/ja.2015.16.
408. S. Marumo, K. Hattori and M. Katayama, Agric. Biol. Chem., 1985, 49, 1521–1522,  DOI:10.1080/00021369.1985.10866933.
409. Y.-B. Zeng, H.-G. Gu, W.-J. Zuo, L.-L. Zhang, H.-J. Bai, Z.-K. Guo, P. Proksch, W.-L. Mei and H.-F. Dai, Arch. Pharmacal Res., 2015, 38, 673–676,  DOI:10.1007/s12272-014-0448-8.
410. J. Wang, S. Huang, C. Li, W. Ding, Z. She and C. Li, Chem. Nat. Compd., 2015, 51, 239–241,  DOI:10.1007/s10600-015-1252-5.
411. T. Bunyapaiboonsri, S. Yoiprommarat, R. Nopgason, K. Intereya, R. Suvannakad and J. Sakayaroj, Tetrahedron, 2015, 71, 5572–5578,  DOI:10.1016/j.tet.2015.06.061.
412. M. Isaka, S. Palasarn, P. Tobwor, T. Boonruangprapa and K. Tasanathai, J. Antibiot., 2012, 65, 571–574,  DOI:10.1038/ja.2012.76.
413. C. F. P. Hemphill, G. Daletos, A. Hamacher, M. U. Kassack, W. Lin, A. Mándi, T. Kurtán and P. Proksch, Tetrahedron Lett., 2015, 56, 4430–4433,  DOI:10.1016/j.tetlet.2015.03.126.
414. Z.-J. Lin, Z.-Y. Lu, T.-J. Zhu, Y.-C. Fang, Q.-Q. Gu and W.-M. Zhu, Chem. Pharm. Bull., 2008, 56, 217–221,  DOI:10.1248/cpb.56.217.
415. K. Kempf, F. Schmitt, U. Bilitewski and R. Schobert, Tetrahedron, 2015, 71, 5064–5068,  DOI:10.1016/j.tet.2015.05.116.
416. X. Li, Y. Yao, Y. Zheng, I. Sattler and W. Lin, Arch. Pharmacal Res., 2007, 30, 812–815,  DOI:10.1007/bf02978829.
417. J. Li, C. Zhao, J. Liu and Y. Du, Tetrahedron, 2015, 71, 3885–3889,  DOI:10.1016/j.tet.2015.04.025.
418. H. Li, J. Jiang, Z. Liu, S. Lin, G. Xia, X. Xia, B. Ding, L. He, Y. Lu and Z. She, J. Nat. Prod., 2014, 77, 800–806,  DOI:10.1021/np400880w.
419. J. T. J. Spence and J. H. George, Org. Lett., 2015, 17, 5970–5973,  DOI:10.1021/acs.orglett.5b02902.
420. Z.-F. Zhou, T. Kurtán, X.-H. Yang, A. Mándi, M.-Y. Geng, B.-P. Ye, O. Taglialatela-Scafati and Y.-W. Guo, Org. Lett., 2014, 16, 1390–1393,  DOI:10.1021/ol5001523.
421. J. H. Kim, S. Lee and S. Kim, Angew. Chem., Int. Ed., 2015, 54, 10875–10878,  DOI:10.1002/anie.201504954.
422. D. Ronsberg, A. Debbab, A. Mandi, V. Wray, H. F. Dai, T. Kurtan, P. Proksch and A. H. Aly, Tetrahedron Lett., 2013, 54, 3256–3259,  DOI:10.1016/j.tetlet.2013.04.031.
423. V. S. Mallula, B. Srinivas and P. R. Krishna, Tetrahedron Lett., 2015, 56, 4711–4713,  DOI:10.1016/j.tetlet.2015.06.009.
424. V. Rukachaisirikul, A. Rodglin, S. Phongpaichit, J. Buatong and J. Sakayaroj, Phytochem. Lett., 2012, 5, 13–17,  DOI:10.1016/j.phytol.2011.08.008.
425. K. Tadpetch, L. Jeanmard and V. Rukachaisirikul, Tetrahedron: Asymmetry, 2015, 26, 918–923,  DOI:10.1016/j.tetasy.2015.06.020.
426. Z. Y. Lu, H. J. Zhu, P. Fu, Y. Wang, Z. H. Zhang, H. P. Lin, P. P. Liu, Y. B. Zhuang, K. Hong and W. M. Zhu, J. Nat. Prod., 2010, 73, 911–914,  DOI:10.1021/np100059m.
427. J. F. Wang, Z. Y. Lu, P. P. Liu, Y. Wang, J. Li, K. Hong and W. M. Zhu, Planta Med., 2012, 78, 1861–1866,  DOI:10.1055/s-0032-1315395.
428. J.-F. Wang, X. Qin, F.-Q. Xu, T. Zhang, S. Liao, X. Lin, B. Yang, J. Liu, L. Wang, Z. Tu and Y. Liu, Nat. Prod. Res., 2015, 29, 1761–1765,  DOI:10.1080/14786419.2014.999061.
429. L. Bornancin, F. Boyaud, Z. Mahiout, I. Bonnard, S. C. Mills, B. Banaigs and N. Inguimbert, Mar. Drugs, 2015, 13, 7285–7300,  DOI:10.3390/md13127065.
430. I. Bonnard, M. Rolland, C. Francisco and B. Banaigs, Lett. Pept. Sci., 1997, 4, 289–292.
431. I. Bonnard, M. Rolland, J. M. Salmon, E. Debiton, C. Barthomeuf and B. Banaigs, J. Med. Chem., 2007, 50, 1266–1279,  DOI:10.1021/jm061307x.
432. F. Boyaud, Z. Mahiout, C. Lenoir, S. B. Tang, J. Wdzieczak-Bakala, A. Witczak, I. Bonnard, B. Banaigs, T. Ye and N. Inguimbert, Org. Lett., 2013, 15, 3898–3901,  DOI:10.1021/ol401645m.
433. O. B. Vining, R. A. Medina, E. A. Mitchell, P. Videau, D. Li, J. D. Serrill, J. X. Kelly, W. H. Gerwick, P. J. Proteau, J. E. Ishmael and K. L. McPhail, J. Nat. Prod., 2015, 78, 413–420,  DOI:10.1021/np5007907.
434. A. Iwasaki, O. Ohno, S. Sumimoto, H. Ogawa, K. Anh Nguyen and K. Suenaga, Org. Lett., 2015, 17, 652–655,  DOI:10.1021/ol5036722.
435. A. Watanabe, O. Ohno, M. Morita, T. Inuzuka and K. Suenaga, Bull. Chem. Soc. Jpn., 2015, 88, 1256–1264,  DOI:10.1246/bcsj.20150117.
436. K. Kleigrewe, J. Almaliti, I. Y. Tian, R. B. Kinnel, A. Korobeynikov, E. A. Monroe, B. M. Duggan, V. D. Marzo, D. H. Sherman, P. C. Dorrestein, L. Gerwick and W. H. Gerwick, J. Nat. Prod., 2015, 78, 1671–1682,  DOI:10.1021/acs.jnatprod.5b00301.
437. P. D. Boudreau, E. A. Monroe, S. Mehrotra, S. Desfor, A. Korobeynikov, D. H. Sherman, T. F. Murray, L. Gerwick, P. C. Dorrestein and W. H. Gerwick, PLoS One, 2015, 10, e0133297,  DOI:10.1371/journal.pone.0133297.
438. D. T. A. Youssef, L. A. Shaala, G. A. Mohamed, S. R. M. Ibrahim, Z. M. Banjar, J. M. Badr, K. L. McPhail, A. L. Risinger and S. L. Mooberry, Nat. Prod. Res., 2015, 29, 703–709,  DOI:10.1080/14786419.2014.982647.
439. P. N. Leão, H. Nakamura, M. Costa, A. R. Pereira, R. Martins, V. Vasconcelos, W. H. Gerwick and E. P. Balskus, Angew. Chem., Int. Ed., 2015, 54, 11063–11067,  DOI:10.1002/anie.201503186.
440. K. Ersmark, Angew. Chem., Int. Ed., 2008, 47, 1202–1223,  DOI:10.1002/anie.200605219.
441. K. Fujii, K. Sivonen, K. Adachi, K. Noguchi, H. Sano, K. Hirayama, M. Suzuki and K. Harada, Tetrahedron Lett., 1997, 38, 5525–5528,  DOI:10.1016/S0040-4039(97)01192-1.
442. L. Liu, A. Budnjo, J. Jokela, B. E. Haug, D. P. Fewer, M. Wahlsten, L. Rouhiainen, P. Permi, T. Fossen and K. Sivonen, ACS Chem. Biol., 2015, 10, 725–733,  DOI:10.1021/cb5004306.
443. C.-L. Shao, R. G. Linington, M. J. Balunas, A. Centeno, P. Boudreau, C. Zhang, N. Engene, C. Spadafora, T. S. Mutka, D. E. Kyle, L. Gerwick, C.-Y. Wang and W. H. Gerwick, J. Org. Chem., 2015, 80, 7849–7855,  DOI:10.1021/acs.joc.5b01264.
444. S. Mori, H. Williams, D. Cagle, K. Karanovich, F. David Horgen, R. Smith III and C. M. H. Watanabe, Mar. Drugs, 2015, 13, 6274–6290,  DOI:10.3390/md13106274.
445. S. Okamoto, A. Iwasaki, O. Ohno and K. Suenaga, J. Nat. Prod., 2015, 78, 2719–2725,  DOI:10.1021/acs.jnatprod.5b00662.
446. A. Iwasaki, O. Ohno, S. Sumimoto, S. Suda and K. Suenaga, RSC Adv., 2014, 4, 12840–12843,  10.1039/c4ra00132j.
447. G. Navarro, S. Cummings, J. Lee, N. Moss, E. Glukhov, F. A. Valeriote, L. Gerwick and W. H. Gerwick, Environ. Sci. Technol. Lett., 2015, 2, 166–170,  DOI:10.1021/acs.estlett.5b00116.
448. M. Yotsu-Yamashita, R. L. Haddock and T. Yasumoto, J. Am. Chem. Soc., 1993, 115, 1147–1148,  DOI:10.1021/ja00056a048.
449. M. Yotsu-Yamashita, T. Seki, V. J. Paul, H. Naoki and T. Yasumoto, Tetrahedron Lett., 1995, 36, 5563–5566,  DOI:10.1016/0040-4039(95)01052-J.
450. M. Yotsu-Yamashita, T. Yasumoto, S. Yamada, F. F. A. Bajarias, M. A. Formeloza, M. L. Romero and Y. Fukuyo, Chem. Res. Toxicol., 2004, 17, 1265–1271,  DOI:10.1021/tx0498556.
451. M. Yotsu-Yamashita, K. Abe, T. Seki, K. Fujiwara and T. Yasumoto, Tetrahedron Lett., 2007, 48, 2255–2259,  DOI:10.1016/j.tetlet.2007.02.003.
452. A. R. Soares, N. Engene, S. P. Gunasekera, J. M. Sneed and V. J. Paul, J. Nat. Prod., 2015, 78, 534–538,  DOI:10.1021/np500598x.
453. L. A. Salvador-Reyes, J. Sneed, V. J. Paul and H. Luesch, J. Nat. Prod., 2015, 78, 1957–1962,  DOI:10.1021/acs.jnatprod.5b00293.
454. R. A. Medina, D. E. Goeger, P. Hills, S. L. Mooberry, N. Huang, L. I. Romero, E. Ortega-Barria, W. H. Gerwick and K. L. McPhail, J. Am. Chem. Soc., 2008, 130, 6324,  DOI:10.1021/ja801383f.
455. G. Yao, Z. Pan, C. Wu, W. Wang, L. Fang and W. Su, J. Am. Chem. Soc., 2015, 137, 13488–13491,  DOI:10.1021/jacs.5b09286.
456. H. Luesch, W. Y. Yoshida, G. G. Harrigan, J. P. Doom, R. E. Moore and V. J. Paul, J. Nat. Prod., 2002, 65, 1945–1948,  DOI:10.1021/np0202879.
457. H. Fuwa, Y. Okuaki, N. Yamagata and M. Sasaki, Angew. Chem., Int. Ed., 2015, 54, 868–873,  DOI:10.1002/anie.201409629.
458. S. Matthew, L. A. Salvador, P. J. Schupp, V. J. Paul and H. Luesch, J. Nat. Prod., 2010, 73, 1544–1552,  DOI:10.1021/np1004032.
459. C.-F. Chang, E. Stefan and R. E. Taylor, Chem.–Eur. J., 2015, 21, 10681–10686,  DOI:10.1002/chem.201502132.
460. L. T. Tan, J. Nat. Prod., 2002, 65, 925–928,  DOI:10.1021/np010526c.
461. A. Iwasaki, O. Ohno, S. Sumimoto, S. Suda and K. Suenaga, Tetrahedron Lett., 2014, 55, 4126–4128,  DOI:10.1016/j.tetlet.2014.05.099.
462. A. Plaza and C. A. Bewley, J. Org. Chem., 2006, 71, 6898–6907,  DOI:10.1021/jo061044e.
463. A. Takayanagi, A. Iwasaki and K. Suenaga, Tetrahedron Lett., 2015, 56, 4947–4949,  DOI:10.1016/j.tetlet.2015.06.090.
464. S. Qu, Y. Chen, X. Wang, S. Chen, Z. Xu and T. Ye, Chem. Commun., 2015, 51, 2510–2513,  10.1039/C4CC08901D.
465. S. Matthew, V. J. Paul and H. Luesch, Planta Med., 2009, 75, 528–533,  DOI:10.1055/s-0029-1185332.
466. H. Choi, E. Mevers, T. Byrum, F. A. Valeriote and W. H. Gerwick, Eur. J. Org. Chem., 2012, 5141–5150,  DOI:10.1002/ejoc.201200691.
467. R. Pirovani, G. Brito, R. Barcelos and R. Pilli, Mar. Drugs, 2015, 13, 3309–3324,  DOI:10.3390/md13063309.
468. H.-S. Kang, A. Krunic and J. Orjala, Tetrahedron Lett., 2012, 53, 3563–3567,  DOI:10.1016/j.tetlet.2012.04.136.
469. J. S. Yadav, B. Suresh and P. Srihari, Eur. J. Org. Chem., 2015, 2015, 5856–5863,  DOI:10.1002/ejoc.201500677.
470. C. M. Pavlik, C. Y. B. Wong, S. Ononye, D. D. Lopez, N. Engene, K. L. McPhail, W. H. Gerwick and M. J. Balunas, J. Nat. Prod., 2013, 76, 2026–2033,  DOI:10.1021/np400198r.
471. Q. Liu, W. Lu, M. Ma, J. Liao, A. Ganesan, Y. Hu, S. Wen and P. Huang, RSC Adv., 2015, 5, 1109–1112,  10.1039/c4ra13889a.
472. D. J. Edwards, B. L. Marquez, L. M. Nogle, K. McPhail, D. E. Goeger, M. A. Roberts and W. H. Gerwick, Chem. Biol., 2004, 11, 817–833,  DOI:10.1016/j.chembiol.2004.03.030.
473. X. Zhu, J. Liu and W. Zhang, Nat. Chem. Biol., 2015, 11, 115–120,  DOI:10.1038/nchembio.1718.
474. K. Taori, V. J. Paul and H. Luesch, J. Am. Chem. Soc., 2008, 130, 1806–1807,  DOI:10.1021/ja7110064.
475. G. R. Pettit, Y. Kamano, C. L. Herald, A. A. Tuinman, F. E. Boettner, H. Kizu, J. M. Schmidt, L. Baczynskyj and K. B. Tomer, J. Am. Chem. Soc., 1987, 109, 6883–6885,  DOI:10.1021/ja00256a070.
476. G. G. Harrigan, H. Luesch, W. Y. Yoshida, R. E. Moore, D. G. Nagle, V. J. Paul, S. L. Mooberry, T. H. Corbett and F. A. Valeriote, J. Nat. Prod., 1998, 61, 1075–1077,  DOI:10.1021/np980321c.
477. L. A. Salvador-Reyes, N. Engene, V. J. Paul and H. Luesch, J. Nat. Prod., 2015, 78, 486–492,  DOI:10.1021/np500931q.
478. K. Kumagai, M. Minamida, M. Akakabe, M. Tsuda, Y. Konishi, A. Tominaga, M. Tsuda, E. Fukushi and J. Kawabata, Bioorg. Med. Chem. Lett., 2015, 25, 635–638,  DOI:10.1016/j.bmcl.2014.12.003.
479. M. Tsuda, K. Kumagai, A. Masuda, E. Fukushi and J. Kawabata, Heterocycles, 2015, 91, 265–274,  DOI:10.3987/com-14-13132.
480. T. Kubota, T. Iwai, H. Ishiyama, K. Sakai, T. Gonoi and J. Kobayashi, Tetrahedron Lett., 2015, 56, 990–993,  DOI:10.1016/j.tetlet.2015.01.058.
481. B. Krock, U. Tillmann, É. Potvin, H. Jeong, W. Drebing, J. Kilcoyne, A. Al-Jorani, M. Twiner, Q. Göthel and M. Köck, Mar. Drugs, 2015, 13, 6687–6702,  DOI:10.3390/md13116687.
482. I. Rodríguez, G. Genta-Jouve, C. Alfonso, K. Calabro, E. Alonso, J. A. Sánchez, A. Alfonso, O. P. Thomas and L. M. Botana, Org. Lett., 2015, 17, 2392–2395,  DOI:10.1021/acs.orglett.5b00902.
483. J. Bordner, W. E. Thiessen, H. A. Bates and H. Rapoport, J. Am. Chem. Soc., 1975, 97, 6008–6012,  DOI:10.1021/ja00854a009.
484. S. Tsuchiya, Y. Cho, K. Konoki, K. Nagasawa, Y. Oshima and M. Yotsu-Yamashita, Org. Biomol. Chem., 2014, 12, 3016–3020,  10.1039/c4ob00071d.
485. S. Tsuchiya, Y. Cho, K. Konoki, K. Nagasawa, Y. Oshima and M. Yotsu-Yamashita, Chem.–Eur. J., 2015, 21, 7835–7840,  DOI:10.1002/chem.201500064.
486. B. D. Mooney, M. de Salas, G. M. Hallegraeff and A. R. Place, J. Phycol., 2009, 45, 164–175,  DOI:10.1111/j.1529-8817.2008.00630.x.
487. J. E. Adolf, T. R. Bachvaroff, A. R. Place and J. R. Deeds, Harmful Algae, 2015, 48, 83–93,  DOI:10.1016/j.hal.2015.07.006.
488. J. Peng, A. R. Place, W. Yoshida, C. Anklin and M. T. Hamann, J. Am. Chem. Soc., 2010, 132, 3277–3279,  DOI:10.1021/ja9091853.
489. A. L. Waters, J. Oh, A. R. Place and M. T. Hamann, Angew. Chem., Int. Ed., 2015, 54, 15705–15710,  DOI:10.1002/anie.201507418.
490. F. Buonanno, Ital. J. Zool., 2005, 72, 293–295,  DOI:10.1080/11250000509356688.
491. Y. Sera, M. Eiraku Masaki, M. Doe, F. Buonanno, A. Miyake, Y. Usuki and H. Iio, Chem. Lett., 2015, 44, 633–635,  DOI:10.1246/cl.150044.
492. H. Nakamura, K. Sawada, H. Araie, I. Suzuki and Y. Shiraiwa, Phytochemistry, 2015, 111, 107–113,  DOI:10.1016/j.phytochem.2014.12.023.
493. H. Onodera, M. Satake, Y. Oshima, T. Yasumoto and W. W. Carmichael, Nat. Toxins, 1997, 5, 146–151,  DOI:10.1002/19970504nt4.
494. Y. Cho, S. Tsuchiya, R. Yoshioka, T. Omura, K. Konoki, Y. Oshima and M. Yotsu-Yamashita, Harmful Algae, 2015, 49, 58–67,  DOI:10.1016/j.hal.2015.09.003.
495. M. Minamida, K. Kumagai, D. Ulanova, M. Akakabe, Y. Konishi, A. Tominaga, H. Tanaka, M. Tsuda, E. Fukushi, J. Kawabata, A. Masuda and M. Tsuda, Org. Lett., 2014, 16, 4858–4861,  DOI:10.1021/ol5023504.
496. R. J. Lewis, M. Sellin, M. Poli, R. S. Norton, J. K. MacLeod and M. M. Sheil, Toxicon, 1991, 29, 1115–1127,  DOI:10.1016/0041-0101(91)90209-a.
497. M. Holmes, D. Kwon, M. Taron and R. Britton, Org. Lett., 2015, 17, 3868–3871,  DOI:10.1021/acs.orglett.5b01844.
498. S. Yamashita, K. Takeuchi, T. Koyama, M. Inoue, Y. Hayashi and M. Hirama, Chem.–Eur. J., 2015, 21, 2621–2628,  DOI:10.1002/chem.201405629.
499. T. Yasumoto, R. Bagnis and J. P. Vernoux, Nippon Suisan Gakkaishi, 1976, 42, 359–365,  DOI:10.2331/suisan.42.359.
500. G. S. Kohli, U. John, R. I. Figueroa, L. L. Rhodes, D. T. Harwood, M. Groth, C. J. S. Bolch and S. A. Murray, BMC Genomics, 2015, 16, 410,  DOI:10.1186/s12864-015-1625-y.
501. K. Nakanishi, Toxicon, 1985, 23, 473–479,  DOI:10.1016/0041-0101(85)90031-5.
502. R. T. Cassell, W. Chen, S. Thomas, L. Liu and K. S. Rein, ChemBioChem, 2015, 16, 1060–1067,  DOI:10.1002/cbic.201402669.
503. A. Iwasaki, O. Ohno, S. Sumimoto, T. Matsubara, S. Shimada, T. Sato and K. Suenaga, J. Nat. Prod., 2015, 78, 901–908,  DOI:10.1021/acs.jnatprod.5b00168.
504. P. Yang, D.-Q. Liu, T.-J. Liang, J. Li, H.-Y. Zhang, A.-H. Liu, Y.-W. Guo and S.-C. Mao, Bioorg. Med. Chem., 2015, 23, 38–45,  DOI:10.1016/j.bmc.2014.11.031.
505. L. Ali, A. Khan, L. Al-Kharusi, J. Hussain and A. Al-Harrasi, Mar. Drugs, 2015, 13, 4344–4356,  DOI:10.3390/md13074344.
506. D. E. Williams, C. M. Sturgeon, M. Roberge and R. J. Andersen, J. Am. Chem. Soc., 2007, 129, 5822,  DOI:10.1021/ja0715187.
507. J. Chen, P. Koswatta, J. R. DeBergh, P. Fu, E. Pan, J. B. MacMillan and J. M. Ready, Chem. Sci., 2015, 6, 2932–2937,  10.1039/c5sc00281h.
508. B. Wang, A. L. Waters, F. A. Valeriote and M. T. Hamann, Biochim. Biophys. Acta, Gen. Subj., 2015, 1850, 1849–1854,  DOI:10.1016/j.bbagen.2015.05.004.
509. V. P. Lorenzo, J. M. B. Filho, L. Scotti and M. T. Scotti, Rev. Bras. Farmacogn., 2015, 25, 690–697,  DOI:10.1016/j.bjp.2015.08.005.
510. H. Wu, H. Niu, A. Shao, C. Wu, B. J. Dixon, J. Zhang, S. Yang and Y. Wang, Mar. Drugs, 2015, 13, 5750–5766,  DOI:10.3390/md13095750.
511. L. Zhang and H. Wang, Mar. Drugs, 2015, 13, 4310–4330,  DOI:10.3390/md13074310.
512. S. Kathiresan, A. Chandrashekar, G. A. Ravishankar and R. Sarada, J. Biotechnol., 2015, 196–197, 33–41,  DOI:10.1016/j.jbiotec.2015.01.006.
513. J. Li, W. Dai, Y. Xia, K. Chen, S. Li, T. Liu, R. Zhang, J. Wang, W. Lu, Y. Zhou, Q. Yin, H. Abudumijiti, R. Chen, Y. Zheng, F. Wang, J. Lu, Y. Zhou and C. Guo, Mar. Drugs, 2015, 13, 6064–6081,  DOI:10.3390/md13106064.
514. A. Andrisani, G. Donà, E. Tibaldi, A. Maria Brunati, C. Sabbadin, D. Armanini, G. Alvisi, S. Gizzo, G. Ambrosini, E. Ragazzi and L. Bordin, Mar. Drugs, 2015, 13, 5533–5551,  DOI:10.3390/md13095533.
515. J.-Y. Wang, Y.-J. Lee, M.-C. Chou, R. Chang, C.-H. Chiu, Y.-J. Liang and L.-S. Wu, Mar. Drugs, 2015, 13, 1375–1388,  DOI:10.3390/md13031375.
516. Z.-S. Li, K. Noda, E. Fujita, Y. Manabe, T. Hirata and T. Sugawara, J. Nutr., 2015, 145, 490–498,  DOI:10.3945/jn.114.200931.
517. Y. Yang, B. Kim, Y.-K. Park, S. I. Koo and J.-Y. Lee, Biochim. Biophys. Acta, 2015, 1850, 178–185,  DOI:10.1016/j.bbagen.2014.10.014.
518. S.-X. Guo, H.-L. Zhou, C.-L. Huang, C.-G. You, Q. Fang, P. Wu, X.-G. Wang and C.-M. Han, Mar. Drugs, 2015, 13, 2105–2123,  DOI:10.3390/md13042105.
519. É. M. Bianco, T. M. Francisco, C. B. Pinheiro, R. B. de Vasconcellos Azeredo, V. L. Teixeira and R. C. Pereira, Helv. Chim. Acta, 2015, 98, 785–794,  DOI:10.1002/hlca.201400321.
520. É. M. Bianco, T. M. Francisco, C. B. Pinheiro, R. B. de Vasconcellos Azeredo, V. L. Teixeira and R. C. Pereira, Chem. Biodiversity, 2015, 12, 1665–1677,  DOI:10.1002/cbdv.201400410.
521. M. Zhao, S. Cheng, W. Yuan, J. Dong, K. Huang, Z. Sun and P. Yan, Chem. Pharm. Bull., 2015, 63, 1081–1086,  DOI:10.1248/cpb.c15-00556.
522. W. M. Alarif, S. A. Basaif, F. A. Badria and S.-E. N. Ayyadd, Chem. Nat. Compd., 2015, 51, 697–702,  DOI:10.1007/s10600-015-1387-4.
523. H.-Y. Fang, U. Chokkalingam, S.-F. Chiou, T.-L. Hwang, S.-L. Chen, W.-L. Wang and J.-H. Sheu, Int. J. Mol. Sci., 2015, 16, 736–746,  DOI:10.3390/ijms16010736.
524. R. Brkljača and S. Urban, Mar. Drugs, 2015, 13, 102–127,  DOI:10.3390/md13010102.
525. R. Brkljača, E. Göker and S. Urban, Mar. Drugs, 2015, 13, 2714–2731,  DOI:10.3390/md13052714.
526. C. Areche, J. Benites, A. Cornejo, L. M. Ruiz, O. García-Beltrán, M. J. Simirgiotis and B. Sepúlveda, Mar. Drugs, 2015, 13, 1726–1738,  DOI:10.3390/md13041726.
527. A. R. Soares, H. M. Duarte, L. W. Tinnoco, R. C. Pereira and V. L. Teixeira, Rev. Bras. Farmacogn., 2015, 25, 627–633,  DOI:10.1016/j.bjp.2015.09.006.
528. M. El Hattab, G. Genta-Jouve, N. Bouzidi, A. Ortalo-Magné, C. Hellio, J.-P. Maréchal, L. Piovetti, O. P. Thomas and G. Culioli, J. Nat. Prod., 2015, 78, 1663–1670,  DOI:10.1021/acs.jnatprod.5b00264.
529. A. G. Gonzalez, J. Darias and J. D. Martin, Tetrahedron Lett., 1971, 12, 2729–2732,  DOI:10.1016/s0040-4039(01)96964-3.
530. F. Sanchez-Ferrando and A. San-Martin, J. Org. Chem., 1995, 60, 1475–1478,  DOI:10.1021/jo00110a062.
531. O. M. M. Sabry, S. Andrews, K. L. McPhail, D. E. Goeger, A. Yokochi, K. T. LePage, T. F. Murray and W. H. Gerwick, J. Nat. Prod., 2005, 68, 1022–1030,  DOI:10.1021/np050051f.
532. A. Gutiérrez-Cepeda, J. J. Fernández, M. Norte, S. Montalvão, P. Tammela and M. L. Souto, J. Nat. Prod., 2015, 78, 1716–1722,  DOI:10.1021/acs.jnatprod.5b00415.
533. A. Miyanaga, N. Funa, T. Awakawa and S. Horinouchi, Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 871–876.
534. C. Hertweck, Angew. Chem., Int. Ed., 2009, 48, 4688–4716,  DOI:10.1002/anie.200806121.
535. J. F. Biard, J. F. Verbist, R. Floch and Y. Letourneux, Tetrahedron Lett., 1980, 21, 1849–1852,  DOI:10.1016/s0040-4039(00)92796-5.
536. A. Ortalo-Magne, G. Culioli, R. Valls, B. Pucci and L. Piovetti, Phytochemistry, 2005, 66, 2316–2323,  DOI:10.1016/j.phytochem.2005.06.006.
537. C. Merten, V. Smyrniotopoulos and D. Tasdemir, Chem. Commun., 2015, 51, 16217–16220,  10.1039/c5cc05659d.
538. P. Crews, T. E. Klein, E. R. Hogue and B. L. Myers, J. Org. Chem., 1982, 47, 811–815,  DOI:10.1021/jo00344a012.
539. L. T. Leung and P. Chiu, Chem.–Asian J., 2015, 10, 1042–1049,  DOI:10.1002/asia.201403325.
540. A. D. Yamaguchi, K. M. Chepiga, J. Yamaguchi, K. Itami and H. M. L. Davies, J. Am. Chem. Soc., 2015, 137, 644–647,  DOI:10.1021/ja512059d.
541. D. Pádua, E. Rocha, D. Gargiulo and A. A. Ramos, Phytochem. Lett., 2015, 14, 91–98,  DOI:10.1016/j.phytol.2015.09.007.
542. K. R. R. Rengasamy, M. G. Kulkarni, W. A. Stirk and J. V. Staden, J. Appl. Phycol., 2015, 27, 581–587,  DOI:10.1007/s10811-014-0337-z.
543. M.-S. Lee, B. Lee, K.-E. Park, T. Utsuki, T. Shin, C. Woong Oh and H.-R. Kim, Food Chem., 2015, 174, 538–546,  DOI:10.1016/j.foodchem.2014.11.090.
544. J.-H. Ahn, Y.-I. Yang, K.-T. Lee and J.-H. Choi, J. Cancer Res. Clin. Oncol., 2015, 141, 255–268,  DOI:10.1007/s00432-014-1819-8.
545. Y.-I. Yang, J.-H. Ahn, Y. Seok Choi and J.-H. Choi, Gynecol. Oncol., 2015, 136, 355–364,  DOI:10.1016/j.ygyno.2014.11.015.
546. C.-S. Kong, H. Kim and Y. Seo, J. Food Biochem., 2015, 39, 1–10,  DOI:10.1111/jfbc.12093.
547. H.-N. You, H.-A. Lee, M.-H. Park, J.-H. Lee and J.-S. Han, Eur. J. Pharmacol., 2015, 752, 92–96,  DOI:10.1016/j.ejphar.2015.02.003.
548. B. W. Choi, H. S. Lee, H.-C. Shin and B. H. Lee, Phytother. Res., 2015, 29, 549–553,  DOI:10.1002/ptr.5282.
549. E.-K. Kim, Y. Tang, Y.-S. Kim, J.-W. Hwang, E.-J. Choi, J.-H. Lee, S.-H. Lee, Y.-J. Jeon and P.-J. Park, Mar. Drugs, 2015, 13, 1785–1797,  DOI:10.3390/md13041785.
550. N.-J. Kang, D.-H. Koo, G.-J. Kang, S.-C. Han, B.-W. Lee, Y.-S. Koh, J.-W. Hyun, N.-H. Lee, M.-H. Ko, H.-K. Kang and E.-S. Yoo, Biomol. Ther., 2015, 23, 238–244,  DOI:10.4062/biomolther.2014.141.
551. T.-H. Kwon, Y.-X. Wu, J.-S. Kim, J.-H. Woo, K. T. Park, O. J. Kwon, H.-J. Seo, T. Kim and N.-H. Park, J. Sci. Food Agric., 2015, 95, 1830–1837,  DOI:10.1002/jsfa.6881.
552. E. Rickert, U. Karsten, G. Pohnert and M. Wahl, Biofouling, 2015, 31, 363–377,  DOI:10.1080/08927014.2015.1041020.
553. J. S. Choi, Y. R. Han, J. S. Byeon, S.-Y. Choung, H. S. Sohn and H. A. Jung, J. Pharm. Pharmacol., 2015, 67, 1170–1178,  DOI:10.1111/jphp.12404.
554. S.-H. Eom, S.-Y. Moon, D.-S. Lee, H.-J. Kim, K. Park, E.-W. Lee, T. H. Kim, Y.-H. Chung, M.-S. Lee and Y.-M. Kim, Algae, 2015, 30, 241–246,  DOI:10.4490/algae.2015.30.3.241.
555. D.-K. Yu, B. Lee, M. Kwon, N. Yoon, T. Shin, N.-G. Kim, J.-S. Choi and H.-R. Kim, Int. Immunopharmacol., 2015, 28, 1068–1075,  DOI:10.1016/j.intimp.2015.08.028.
556. H. Kurihara, R. Konno and K. Takahashi, Biosci., Biotechnol., Biochem., 2015, 79, 1954–1956,  DOI:10.1080/09168451.2015.1062716.
557. J.-H. Lee, J.-Y. Ko, J.-Y. Oh, E.-A. Kim, C.-Y. Kim and Y.-J. Jeon, Algae, 2015, 30, 313–323,  DOI:10.4490/algae.2015.30.4.313.
558. H. Maeda, J. Oleo Sci., 2015, 64, 125–132,  DOI:10.5650/jos.ess14226.
559. L. J. Martin, Mar. Drugs, 2015, 13, 4784–4798,  DOI:10.3390/md13084784.
560. M. A. Gammone and N. D'Orazio, Mar. Drugs, 2015, 13, 2196–2214,  DOI:10.3390/md13042196.
561. H. Maeda, S. Kanno, M. Kodate, M. Hosokawa and K. Miyashita, Mar. Drugs, 2015, 13, 4799–4813,  DOI:10.3390/md13084799.
562. K. Takahashi, M. Hosokawa, H. Kasajima, K. Hatanaka, K. Kudo, N. Shimoyama and K. Miyashita, Oncol. Lett., 2015, 10, 1463–1467,  DOI:10.3892/ol.2015.3380.
563. M.-T. Feng, X.-Q. Yu, P. Yang, H. Yang, K. Lin and S.-C. Mao, Chem. Nat. Compd., 2015, 51, 418–422,  DOI:10.1007/s10600-015-1306-8.
564. T. O. Ronson, M. J. Burns, M. H. H. Voelkel, K. J. Evans, J. M. Lynam, R. J. K. Taylor and I. J. S. Fairlamb, Chem.–Eur. J., 2015, 21, 18905–18909,  DOI:10.1002/chem.20150408.
565. L. Hoffmeister, T. Fukuda, G. Pototschnig and A. Fürstner, Chem.–Eur. J., 2015, 21, 4529–4533,  DOI:10.1002/chem.201500437.
566. F. Cen-Pacheco, A. J. Santiago-Benítez, C. García, S. J. Álvarez-Méndez, A. J. Martín-Rodríguez, M. Norte, V. S. Martín, J. A. Gavín, J. J. Fernández and A. H. Daranas, J. Nat. Prod., 2015, 78, 712–721,  DOI:10.1021/np5008922.
567. O. A. Mukhina, H. Koshino, M. T. Crimmins and A. G. Kutateladze, Tetrahedron Lett., 2015, 56, 4900–4903,  DOI:10.1016/j.tetlet.2015.06.078.
568. M. Rahelivao, M. Gruner, H. Andriamanantoanina, B. Andriamihaja, I. Bauer and H.-J. Knölker, Mar. Drugs, 2015, 13, 4197–4216,  DOI:10.3390/md13074197.
569. T. Kamada and C. S. Vairappan, Nat. Prod. Commun., 2015, 10, 843–847.
570. X.-L. Li, W.-F. He, J. Li, L.-F. Lan, X.-W. Li and Y.-W. Guo, J. Asian Nat. Prod. Res., 2015, 17, 1146–1152,  DOI:10.1080/10286020.2015.1102135.
571. V. Smyrniotopoulos, R. Kiss, V. Mathieu, C. Vagias and V. Roussis, Eur. J. Org. Chem., 2015, 2015, 2848–2853,  DOI:10.1002/ejoc.201500133.
572. D. Rodrigues, C. Alves, A. Horta, S. Pinteus, J. Silva, G. Culioli, O. Thomas and R. Pedrosa, Mar. Drugs, 2015, 13, 713–726,  DOI:10.3390/md13020713.
573. A. Hartmann, K. Becker, U. Karsten, D. Remias and M. Ganzera, Mar. Drugs, 2015, 13, 6291–6305,  DOI:10.3390/md13106291.
574. S. Pidot, K. Ishida, M. Cyrulies and C. Hertweck, Angew. Chem., Int. Ed., 2014, 53, 7856–7859,  DOI:10.1002/anie.201402632.
575. K. Wolkenstein, H. Sun, H. Falk and C. Griesinger, J. Am. Chem. Soc., 2015, 137, 13460–13463,  DOI:10.1021/jacs.5b08191.
576. M. A. Timmers, D. A. Dias and S. Urban, Mar. Drugs, 2012, 10, 2089–2102,  DOI:10.3390/md10092089.
577. C. Bucher, R. M. Deans and N. Z. Burns, J. Am. Chem. Soc., 2015, 137, 12784–12787,  DOI:10.1021/jacs.5b08398.
578. D. J. Kennedy, I. A. Selby, H. J. Cowe, P. J. Cox and R. H. Thomson, J. Chem. Soc., Chem. Commun., 1984, 153–155,  10.1039/c39840000153.
579. T.-i. Sohn, D. Kim and R. S. Paton, Chem.–Eur. J., 2015, 21, 15988–15997,  DOI:10.1002/chem.201502592.
580. K. Kurata and T. Amiya, Chem. Lett., 1977, 1435–1438,  DOI:10.1246/cl.1977.1435.
581. H. Kurihara, T. Mitani, J. Kawabata and K. Takahashi, J. Nat. Prod., 1999, 62, 882–884,  DOI:10.1021/np980324p.
582. N. Wu, J. Luo, B. Jiang, L. Wang, S. Wang, C. Wang, C. Fu, J. Li and D. Shi, Mar. Drugs, 2015, 13, 1010–1025,  DOI:10.3390/md13021010.
583. S. Wang, L.-J. Wang, B. Jiang, N. Wu, X. Li, S. Liu, J. Luo and D. Shi, Int. J. Mol. Sci., 2015, 16, 13548–13560,  DOI:10.3390/ijms160613548.
584. X. Qi, G. Liu, L. Qiu, X. Lin and M. Liu, Biomed. Pharmacother., 2015, 75, 58–66,  DOI:10.1016/j.biopha.2015.08.033.
585. J. Tanaka, T. Higa, G. Benardinelli and C. W. Jefford, Tetrahedron, 1989, 45, 7301–7310,  DOI:10.1016/S0040-4020(01)89191-2.
586. D. E. DeGroot, D. G. Franks, T. Higa, J. Tanaka, M. E. Hahn and M. S. Denison, Chem. Res. Toxicol., 2015, 28, 1176–1185,  DOI:10.1021/acs.chemrestox.5b00003.
587. E. E. Eltamany, A. K. Ibrahim, M. M. Radwan, M. A. ElSohly, H. A. Hassanean and S. A. Ahmed, Med. Chem. Res., 2015, 24, 3467–3473,  DOI:10.1007/s00044-015-1394-9.
588. E. A. Santalova, V. A. Denisenko, P. S. Dmitrenok, A. L. Drozdov and V. A. Stonik, Lipids, 2015, 50, 57–69,  DOI:10.1007/s11745-014-3974-8.
589. E. A. Santalova, V. A. Denisenko and P. S. Dmitrenok, Lipids, 2015, 50, 1209–1218,  DOI:10.1007/s11745-015-4077-x.
590. K. Lin, P. Yang, H. Yang, A.-H. Liu, L.-G. Yao, Y.-W. Guo and S.-C. Mao, Lipids, 2015, 50, 697–703,  DOI:10.1007/s11745-015-4028-6.
591. R. Huang, Y. Chen, X. Zhou, X. Yang and Y. Liu, Chem. Nat. Compd., 2015, 51, 540–541,  DOI:10.1007/s10600-015-1335-3.
592. C. Zhao, Q. Gu, W.-G. Xu, G.-S. Xing, D.-J. Jin, R. Xu, H. Li, H.-Q. Duan, J. Zhou and S.-A. Tang, J. Asian Nat. Prod. Res., 2015, 17, 114–119,  DOI:10.1080/10286020.2014.985769.
593. D. T. A. Youssef, J. M. Badr, L. A. Shaala, G. A. Mohamed and F. H. Bamanie, Phytochem. Lett., 2015, 12, 296–301,  DOI:10.1016/j.phytol.2015.04.024.
594. W.-F. He, L.-F. Liang, Y.-S. Cai, L.-X. Gao, Y.-F. Li, J. Li, H.-L. Liu and Y.-W. Guo, J. Asian Nat. Prod. Res., 2015, 17, 861–866,  DOI:10.1080/10286020.2015.1026334.
595. V. Peddie, K. Takada, S. Okuda, Y. Ise, Y. Morii, N. Yamawaki, T. Takatani, O. Arakawa, S. Okada and S. Matsunaga, J. Nat. Prod., 2015, 78, 2808–2813,  DOI:10.1021/acs.jnatprod.5b00795.
596. U. Abdelmohsen, C. Cheng, A. Reimer, V. Kozjak-Pavlovic, A. Ibrahim, T. Rudel, U. Hentschel, R. A. Edrada-Ebel and S. Ahmed, Planta Med., 2015, 81, 382–387,  DOI:10.1055/s-0035-1545721.
597. A. F. Gabriel, Z. Li, R. Kusuda, C. Tanaka and T. Miyamoto, Chem. Pharm. Bull., 2015, 63, 469–475,  DOI:10.1248/cpb.c15-00203.
598. E. Takanashi, K. Takada, M. Hashimoto, Y. Itoh, Y. Ise, S. Ohtsuka, S. Okada and S. Matsunaga, Tetrahedron, 2015, 71, 9564–9570,  DOI:10.1016/j.tet.2015.10.062.
599. S.-E. N. Ayyad, D. F. Katoua, W. M. Alarif, T. R. Sobahi, M. M. Aly, L. A. Shaala and M. A. Ghandourah, Z. Naturforsch., C: J. Biosci., 2015, 70, 297–303,  DOI:10.1515/znc-2015-5015.
600. X. Wang, B. M. Duggan and T. F. Molinski, J. Am. Chem. Soc., 2015, 137, 12343–12351,  DOI:10.1021/jacs.5b07858.
601. A. F. Barrero, J. E. Oltra, M. M. Herrador, E. Cabrera, J. F. Sanchez, J. Quilex, F. J. Rojas and J. F. Reyes, Tetrahedron, 1993, 49, 141–150,  DOI:10.1016/S0040-4020(01)80514-7.
602. Y. Li, H. Tang, X. Tian, H. Lin, M. Wang and M. Yao, Fitoterapia, 2015, 106, 226–230,  DOI:10.1016/j.fitote.2015.09.012.
603. E. A. Santos, A. L. Quintela, E. G. Ferreira, T. S. Sousa, F. das C. L. Pinto, E. Hajdu, M. S. Carvalho, S. Salani, D. D. Rocha, D. V. Wilke, M. d. C. M. Torres, P. C. Jimenez, E. R. Silveira, J. J. La Clair, O. D. L. Pessoa and L. V. Costa-Lotufo, J. Nat. Prod., 2015, 78, 996–1004,  DOI:10.1021/np5008944.
604. T. R. Hoye, W. M. Alarif, S. S. Basaif, M. Abo-Elkarm, M. T. Hamann, A. E. Wahba and S.-E. N. Ayyad, ARKIVOC, 2015, 2015, 164–175,  DOI:10.3998/ark.5550190.p008.948.
605. M. Gushiken, I. Kagiyama, H. Kato, T. Kuwana, F. Losung, R. E. P. Mangindaan, N. J. de Voogd and S. Tsukamoto, J. Nat. Med., 2015, 69, 595–600,  DOI:10.1007/s11418-015-0920-x.
606. G. Chianese, B.-B. Gu, F. Yang, W.-H. Jiao, Y.-W. Guo, H.-W. Lin and O. Taglialatela-Scafati, RSC Adv., 2015, 5, 63372–63376,  10.1039/c5ra09840h.
607. M. AlTarabeen, A. Hassan Aly, C. Francis Perez Hemphill, M. Rasheed, V. Wray and P. Proksch, Z. Naturforsch., C: J. Biosci., 2015, 70, 75–78,  DOI:10.1515/znc-2014-4197.
608. R. R. Kulkarni, A. Reum Jo, Y. Ho Kim and M. K. Na, Nat. Prod. Sci., 2015, 21, 293–296,  DOI:10.20307/nps.2015.21.4.293.
609. H. Yamazaki, O. Takahashi, S.-i. Kanno, T. Nakazawa, S. Takahashi, K. Ukai, D. A. Sumilat, M. Ishikawa and M. Namikoshi, Bioorg. Med. Chem., 2015, 23, 797–802,  DOI:10.1016/j.bmc.2014.12.049.
610. S. Khokhar, Y. Feng, A. R. Carroll, M. R. Campitelli, R. J. Quinn, J. N. A. Hooper, M. G. Ekins and R. A. Davis, Tetrahedron, 2015, 71, 6204–6209,  DOI:10.1016/j.tet.2015.06.087.
611. G. Esposito, R. Teta, R. Miceli, L. Ceccarelli, G. D. Sala, R. Camerlingo, E. Irollo, A. Mangoni, G. Pirozzi and V. Costantino, Mar. Drugs, 2015, 13, 444–459,  DOI:10.3390/md13010444.
612. K. Fukuhara, K. Takada, S. Okada and S. Matsunaga, Org. Lett., 2015, 17, 2646–2648,  DOI:10.1021/acs.orglett.5b01020.
613. S. R. M. Ibrahim, C. C. Min, F. Teuscher, R. Ebel, C. Kakoschke, W. H. Lin, V. Wray, R. Edrada-Ebel and P. Proksch, Bioorg. Med. Chem., 2010, 18, 4947–4956,  DOI:10.1016/j.bmc.2010.06.012.
614. S. R. M. Ibrahim, R. Edrada-Ebel, G. A. Mohamed, D. T. A. Youssef, V. Wray and P. Proksch, ARKIVOC, 2008, 164–171,  DOI:10.3998/ark.5550190.0009.c18.
615. G. Daletos, R. Kalscheuer, H. Koliwer-Brandl, R. Hartmann, N. J. de Voogd, V. Wray, W. Lin and P. Proksch, J. Nat. Prod., 2015, 78, 1910–1925,  DOI:10.1021/acs.jnatprod.5b00266.
616. H. J. Shin, M. A. Rashid, L. K. Cartner, H. R. Bokesch, J. A. Wilson, J. B. McMahon and K. R. Gustafson, Tetrahedron Lett., 2015, 56, 4215–4219,  DOI:10.1016/j.tetlet.2015.05.058.
617. H. J. Shin, M. A. Rashid, L. K. Cartner, H. R. Bokesch, J. A. Wilson, J. B. McMahon and K. R. Gustafson, Tetrahedron Lett., 2015, 56, 5482,  DOI:10.1016/j.tetlet.2015.08.034.
618. A. Lorente, A. Gil, R. Fernández, C. Cuevas, F. Albericio and M. Álvarez, Chem.–Eur. J., 2015, 21, 150–156,  DOI:10.1002/chem.201404341.
619. D. Youssef, L. Shaala and K. Alshali, Mar. Drugs, 2015, 13, 6609–6619,  DOI:10.3390/md13116609.
620. A. Al-Mourabit, R. Laville, T. Binh Nguyen, C. Moriou, S. Petek and C. Debitus, Heterocycles, 2015, 90, 1351–1366,  DOI:10.3987/com-14-s(k)87.
621. Q. Wang, X. Tang, X. Luo, N. J. de Voogd, P. Li and G. Li, Org. Lett., 2015, 17, 3458–3461,  DOI:10.1021/acs.orglett.5b01503.
622. Z. Liang, F. J. Sulzmaier, W. Y. Yoshida, M. Kelly, J. W. Ramos and P. G. Williams, J. Nat. Prod., 2015, 78, 543–547,  DOI:10.1021/np500759r.
623. M. AlTarabeen, G. Daletos, W. Ebrahim, W. E. G. Müller, R. Hartmann, W. Lin and P. Proksch, Nat. Prod. Commun., 2015, 10, 1951–1954.
624. L. K. Shubina, T. N. Makarieva, D. V. Yashunsky, N. E. Nifantiev, V. A. Denisenko, P. S. Dmitrenok, S. A. Dyshlovoy, S. N. Fedorov, V. B. Krasokhin, S. Hun Jeong, J. Han and V. A. Stonik, J. Nat. Prod., 2015, 78, 1383–1389,  DOI:10.1021/acs.jnatprod.5b00256.
625. D. B. Abdjul, H. Yamazaki, K. Ukai and M. Namikoshi, J. Nat. Med., 2015, 69, 416–420,  DOI:10.1007/s11418-015-0891-y.
626. N. Hanif, K. Yamada, M. Kitamura, Y. Kawazoe, N. J. de Voogd and D. Uemura, Chem. Nat. Compd., 2015, 51, 1130–1133,  DOI:10.1007/s10600-015-1508-0.
627. I. Yang, H. Choi, S.-J. Nam and H. Kang, Bull. Korean Chem. Soc., 2015, 36, 2120–2123,  DOI:10.1002/bkcs.10372.
628. J.-H. Gan, W.-Z. Hu, H.-B. Yu, F. Yang, M.-X. Cao, H.-J. Shi, Y.-F. Kang and B.-N. Han, J. Asian Nat. Prod. Res., 2015, 17, 1231–1238,  DOI:10.1080/10286020.2015.1118465.
629. S. Aoki, H. Wei, K. Matsui, R. Rachmat and M. Kobayashi, Bioorg. Med. Chem., 2003, 11, 1969–1973,  DOI:10.1016/s0968-0896(03)00086-5.
630. E. C. Barnes, N. A. B. M. Said, E. D. Williams, J. N. A. Hooper and R. A. Davis, Tetrahedron, 2010, 66, 283–287,  DOI:10.1016/j.tet.2009.10.109.
631. D. A. Pedrazzoli Moran, K. Takada, Y. Ise, N. Bontemps, R. A. Davis, K. Furihata, S. Okada and S. Matsunaga, Tetrahedron, 2015, 71, 5013–5018,  DOI:10.1016/j.tet.2015.05.070.
632. E. Gros, M.-T. Martin, J. Sorres, C. Moriou, J. Vacelet, M. Frederich, M. Aknin, Y. Kashman, A. Gauvin-Bialecki and A. Al-Mourabit, Chem. Biodiversity, 2015, 12, 1725–1733,  DOI:10.1002/cbdv.201400350.
633. M. T. Jamison and T. F. Molinski, J. Nat. Prod., 2015, 78, 557–561,  DOI:10.1021/np501052a.
634. M. F. C. Santos, P. M. Harper, D. E. Williams, J. T. Mesquita, É. G. Pinto, T. A. da Costa-Silva, E. Hajdu, A. G. Ferreira, R. A. Santos, P. J. Murphy, R. J. Andersen, A. G. Tempone and R. G. S. Berlinck, J. Nat. Prod., 2015, 78, 1101–1112,  DOI:10.1021/acs.jnatprod.5b00070.
635. K. M. Tabakmakher, T. N. Makarieva, V. A. Denisenko, A. G. Guzii, P. S. Dmitrenok, A. S. Kuzmich and V. A. Stonik, Nat. Prod. Commun., 2015, 10, 913–919.
636. S. S. Ebada, M. H. Linh, A. Longeon, N. J. de Voogd, E. Durieu, L. Meijer, M.-L. Bourguet-Kondracki, A. N. B. Singab, W. E. G. Müller and P. Proksch, Nat. Prod. Res., 2015, 29, 231–238,  DOI:10.1080/14786419.2014.947496.
637. C. Schroif-Grégoire, J. Appenzeller, C. Debitus, A. Zaparucha and A. Al-Mourabit, Tetrahedron, 2015, 71, 3609–3613,  DOI:10.1016/j.tet.2014.12.081.
638. T. Kusama, N. Tanaka, Y. Kashiwada and J. Kobayashi, Tetrahedron Lett., 2015, 56, 4502–4504,  DOI:10.1016/j.tetlet.2015.05.114.
639. J. Kobayashi, K. Nakamura, T. Kusama, N. Tanaka, K. Sakai, T. Gonoi and J. Fromont, Heterocycles, 2015, 90, 425–431,  DOI:10.3987/com-14-s(k)38.
640. C. Cychon, E. Lichte and M. Köck, Beilstein J. Org. Chem., 2015, 11, 2029–2037,  DOI:10.3762/bjoc.11.220.
641. T. Kubota, S. Watase, K. Sakai, J. Fromont, T. Gonoi and J. Kobayashi, Bioorg. Med. Chem. Lett., 2015, 25, 5221–5223,  DOI:10.1016/j.bmcl.2015.09.061.
642. L. A. Shaala, D. T. A. Youssef, J. M. Badr, M. Sulaiman, A. Khedr and K. A. El Sayed, Tetrahedron, 2015, 71, 7837–7841,  DOI:10.1016/j.tet.2015.08.024.
643. M. P. Gotsbacher and P. Karuso, Mar. Drugs, 2015, 13, 1389–1409,  DOI:10.3390/md13031389.
644. N. Sirimangkalakitti, O. J. Olatunji, K. Changwichit, T. Saesong, S. Chamni, P. Chanvorachote, K. Ingkaninan, A. Plubrukarn and K. Suwanborirux, Nat. Prod. Commun., 2015, 10, 1945–1949.
645. L. A. Shaala, D. T. A. Youssef, J. M. Badr, M. Sulaiman and A. Khedr, Mar. Drugs, 2015, 13, 1621–1631,  DOI:10.3390/md13041621.
646. Q. Göthel, T. Sirirak and M. Köck, Beilstein J. Org. Chem., 2015, 11, 2334–2342,  DOI:10.3762/bjoc.11.254.
647. C.-K. Kim, J.-K. Woo, S.-H. Kim, E. Cho, Y.-J. Lee, H.-S. Lee, C. J. Sim, D.-C. Oh, K.-B. Oh and J. Shin, J. Nat. Prod., 2015, 78, 2814–2821,  DOI:10.1021/acs.jnatprod.5b00867.
648. W.-H. Jiao, T.-T. Xu, B.-B. Gu, G.-H. Shi, Y. Zhu, F. Yang, B.-N. Han, S.-P. Wang, Y.-S. Li, W. Zhang, J. Li and H.-W. Lin, RSC Adv., 2015, 5, 87730–87738,  10.1039/c5ra18876h.
649. W.-H. Jiao, T.-T. Xu, F. Zhao, H. Gao, G.-H. Shi, J. Wang, L.-L. Hong, H.-B. Yu, Y.-S. Li, F. Yang and H.-W. Lin, Eur. J. Org. Chem., 2015, 2015, 960–966,  DOI:10.1002/ejoc.201403487.
650. H. Hwang, J. Oh, W. Zhou, S. Park, J.-H. Kim, A. G. Chittiboyina, D. Ferreira, G. Y. Song, S. Oh, M. K. Na and M. T. Hamann, J. Nat. Prod., 2015, 78, 453–461,  DOI:10.1021/np500843m.
651. B. N. Ravi, H. P. Perzanowski, R. A. Ross, T. R. Erdman, P. J. Scheuer, J. Finer and J. Clardy, Pure Appl. Chem., 1979, 51, 1893–1900,  DOI:10.1351/pac197951091893.
652. K. Hagiwara, J. E. Garcia Hernandez, M. K. Harper, A. Carroll, C. A. Motti, J. Awaya, H.-Y. Nguyen and A. D. Wright, J. Nat. Prod., 2015, 78, 325–329,  DOI:10.1021/np500793g.
653. F. He, L. Mai, A. Longeon, B. Copp, N. Loaëc, A. Bescond, L. Meijer and M.-L. Bourguet-Kondracki, Mar. Drugs, 2015, 13, 2617–2628,  DOI:10.3390/md13052617.
654. D. B. Abdjul, H. Yamazaki, S.-i. Kanno, O. Takahashi, R. Kirikoshi, K. Ukai and M. Namikoshi, J. Nat. Prod., 2015, 78, 1428–1433,  DOI:10.1021/acs.jnatprod.5b00375.
655. J.-S. Lee, D. B. Abdjul, H. Yamazaki, O. Takahashi, R. Kirikoshi, K. Ukai and M. Namikoshi, Bioorg. Med. Chem. Lett., 2015, 25, 3900–3902,  DOI:10.1016/j.bmcl.2015.07.039.
656. A. Noda, E. Sakai, H. Kato, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, H. Yokosawa and S. Tsukamoto, Bioorg. Med. Chem. Lett., 2015, 25, 2650–2653,  DOI:10.1016/j.bmcl.2015.04.075.
657. N. T. Cue, H. Le T. Anh, D. T. T. Hang, N. X. Nhiem, N. H. Dang, N. H. Nama, P. H. Yen, Do C. Thung, V. K. Thuc, C. V. Minh and P. V. Kiema, Nat. Prod. Commun., 2015, 10, 1341–1343.
658. N. X. Nhiem, N. T. Cuc, D. T. T. Hang, Do T. Trang, N. H. Nam, P. H. Yen, D. C. Thung, Vu K. Thu, H. L. T. Anh, B. H. Tai, C. V. Minh and P. V. Kiem, Magn. Reson. Chem., 2015, 53, 1057–1060,  DOI:10.1002/mrc.4288.
659. J. Kobayashi, N. Tanaka, S. Suto, M. Asai, T. Kusama, A. Takahashi-Nakaguchi, T. Gonoi and J. Fromont, Heterocycles, 2015, 90, 173–185,  DOI:10.3987/com-14-s(k)2.
660. G.-f. Wang, R.-h. Ji, M.-x. Cao, W.-z. Tang, H.-b. Yu, B.-b. Gu, L.-j. Ding, S. Peng, W.-h. Jiao, F. Sun, H.-w. Lin, S.-j. Piao and F. Yang, Chem. Pharm. Bull., 2015, 63, 438–442,  DOI:10.1248/cpb.c15-00022.
661. H. Kato, T. Nehira, K. Matsuo, T. Kawabata, Y. Kobashigawa, H. Morioka, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, H. Yokosawa and S. Tsukamoto, Tetrahedron, 2015, 71, 6956–6960,  DOI:10.1016/j.tet.2015.07.009.
662. J. M. Barber, D. C. Leahy, J. H. Miller and P. T. Northcote, Tetrahedron Lett., 2015, 56, 6314–6318,  DOI:10.1016/j.tetlet.2015.06.013.
663. E. Avilés, J. Prudhomme, K. G. Le Roch and A. D. Rodríguez, Tetrahedron, 2015, 71, 487–494,  DOI:10.1016/j.tet.2014.11.060.
664. J. D. Dattelbaum, A. Jonathan Singh, J. J. Field, J. H. Miller and P. T. Northcote, J. Org. Chem., 2015, 80, 304–312,  DOI:10.1021/jo502370b.
665. J.-K. Woo, J.-e. Jeon, B. Kim, C. J. Sim, D.-C. Oh, K.-B. Oh and J. Shin, Nat. Prod. Sci., 2015, 21, 237–239,  DOI:10.20307/nps.2015.21.4.237.
666. T. Hamada, D. Harada, M. Hirata, K. Yamashita, K. Palaniveloo, H. Okamura, T. Iwagawa, N. Arima, T. Iriguchi, N. J. de Voogd and C. S. Vairappan, Nat. Prod. Commun., 2015, 10, 863–867.
667. T.-R. Su, Z.-J. Liao, M.-C. Lu, Y.-J. Wu and J.-H. Su, Bull. Chem. Soc. Jpn., 2015, 88, 176–182,  DOI:10.1246/bcsj.20140251.
668. J.-W. Lee, H.-S. Lee, J. Shin, J. Soon Kang, J. Yun, H. Jae Shin, J. Seok Lee and Y.-J. Lee, Arch. Pharmacal Res., 2015, 38, 1005–1010,  DOI:10.1007/s12272-014-0479-1.
669. Y.-Y. Lai, M.-C. Lu, L.-H. Wang, J.-J. Chen, L.-S. Fang, Y.-C. Wu and P.-J. Sung, Mar. Drugs, 2015, 13, 4296–4309,  DOI:10.3390/md13074296.
670. Y.-Y. Lai, L.-C. Chen, C.-F. Wu, M.-C. Lu, Z.-H. Wen, T.-Y. Wu, L.-S. Fang, L.-H. Wang, Y.-C. Wu and P.-J. Sung, Int. J. Mol. Sci., 2015, 16, 21950–21958,  DOI:10.3390/ijms160921950.
671. M. H. A. Hassan, M. E. Rateb, M. Hetta, T. A. Abdelaziz, M. A. Sleim, M. Jaspars and R. Mohammed, Tetrahedron, 2015, 71, 577–583,  DOI:10.1016/j.tet.2014.12.035.
672. I. Yang, S.-J. Nam and H. Kang, Nat. Prod. Sci., 2015, 21, 289–292,  DOI:10.20307/nps.2015.21.4.289.
673. F. Cao, Z.-H. Wu, C.-L. Shao, S. Pang, X.-Y. Liang, N. J. de Voogd and C.-Y. Wang, Org. Biomol. Chem., 2015, 13, 4016–4024,  10.1039/c4ob02532f.
674. D. B. Abdjul, H. Yamazaki, O. Takahashi, R. Kirikoshi, R. E. P. Mangindaan and M. Namikoshi, Bioorg. Med. Chem. Lett., 2015, 25, 904–907,  DOI:10.1016/j.bmcl.2014.12.058.
675. J.-K. Woo, C.-K. Kim, C.-H. Ahn, D.-C. Oh, K.-B. Oh and J. Shin, J. Nat. Prod., 2015, 78, 218–224,  DOI:10.1021/np500753q.
676. K. Lee and J.-R. Rho, J. Korean Magn. Reson. Soc., 2015, 19, 23–28,  DOI:10.6564/JKMRS.2015.19.1.023.
677. B. Mun, W. Wang, H. Kim, D. Hahn, I. Yang, D. H. Won, E.-h. Kim, J. Lee, C. Han, H. Kim, M. Ekins, S.-J. Nam, H. Choi and H. Kang, Arch. Pharmacal Res., 2015, 38, 18–25,  DOI:10.1007/s12272-014-0480-8.
678. V. Smyrniotopoulos, M. Rae, S. Soldatou, Y. Ding, C. W. Wolff, G. McCormack, C. M. Coleman, D. Ferreira and D. Tasdemir, Mar. Drugs, 2015, 13, 1632–1646,  DOI:10.3390/md13041632.
679. I. Yang, H. Choi, S.-J. Nam and H. Kang, Arch. Pharmacal Res., 2015, 38, 1970–1974,  DOI:10.1007/s12272-015-0620-9.
680. D. H. R. Barton, R. S. Hay Motherwell and W. B. Motherwell, J. Chem. Soc., Perkin Trans. 1, 1981, 2363–2367,  10.1039/p19810002363.
681. W. Wang, T. Gu Lee, R. S. Patil, B. Mun, I. Yang, H. Kim, D. Hahn, D. H. Won, J. Lee, Y. Lee, H. Choi, S.-J. Nam and H. Kang, J. Nat. Prod., 2015, 78, 368–373,  DOI:10.1021/np500760v.
682. E. G. Lyakhova, S. A. Kolesnikova, A. I. Kalinovsky, P. S. Dmitrenok, N. H. Nam and V. A. Stonik, Steroids, 2015, 96, 37–43,  DOI:10.1016/j.steroids.2015.01.009.
683. G. Genta-Jouve, C. Boughanem, O. Ocaña, T. Pérez and O. P. Thomas, Phytochem. Lett., 2015, 13, 252–255,  DOI:10.1016/j.phytol.2015.07.004.
684. D. Q. Xue, S. C. Mao, X. Q. Yu and Y. W. Guo, Biochem. Syst. Ecol., 2013, 49, 101–106,  DOI:10.1016/j.bse.2013.03.001.
685. D. M. Roll, C. W. J. Chang, P. J. Scheuer, G. A. Gray, J. N. Shoolery and G. K. Matsumoto, J. Am. Chem. Soc., 1985, 107, 2916–2920,  DOI:10.1021/ja00296a014.
686. A. Mándi, I. Wayan Mudianta, T. Kurtán and M. J. Garson, J. Nat. Prod., 2015, 78, 2051–2056,  DOI:10.1021/acs.jnatprod.5b00369.
687. V. Costantino, E. Fattorusso, A. Mangoni and M. Pansini, Steroids, 1995, 60, 768–772,  DOI:10.1016/0039-128x(95)00117-9.
688. Y. Yaoita, M. Kikuchi and K. Machida, Nat. Prod. Commun., 2015, 10, 881–884.
689. R. Capon, E. L. Ghisalberti, P. R. Jefferies, B. W. Skelton and A. H. White, J. Chem. Soc., Perkin Trans. 1, 1981, 2464–2467,  10.1039/p19810002464.
690. G. M. Sharma and B. Vig, Tetrahedron Lett., 1972, 1715–1718,  DOI:10.1016/s0040-4039(01)84729-8.
691. A. Yamashita, Y. Fujimoto, M. Tamaki, A. Setiawan, T. Tanaka, K. Okuyama-Dobashi, H. Kasai, K. Watashi, T. Wakita, M. Toyama, M. Baba, N. de Voogd, S. Maekawa, N. Enomoto, J. Tanaka and K. Moriishi, Mar. Drugs, 2015, 13, 6759–6773,  DOI:10.3390/md13116759.
692. E. A. Jares-Erijman, A. A. Ingrum, F. Sun and K. L. Rinehart, J. Nat. Prod., 1993, 56, 2186–2188,  DOI:10.1021/np50102a025.
693. S. Bondu, G. Genta-Jouve, M. Leiros, C. Vale, J. M. Guigonis, L. M. Botana and O. P. Thomas, RSC Adv., 2012, 2, 2828–2835,  10.1039/c2ra00045h.
694. M. Roel, J. A. Rubiolo, E. Ternon, O. P. Thomas, M. R. Vieytes and L. M. Botana, Mar. Drugs, 2015, 13, 4633–4653,  DOI:10.3390/md13084633.
695. R. Kazlauskas, R. O. Lidgard, P. T. Murphy, R. J. Wells and J. F. Blount, Aust. J. Chem., 1981, 34, 765–786,  DOI:10.1071/ch9810765.
696. K. Eguchi, H. Kato, Y. Fujiwara, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, M. Takeya and S. Tsukamoto, Bioorg. Med. Chem. Lett., 2015, 25, 5389–5392,  DOI:10.1016/j.bmcl.2015.09.024.
697. A. Casapullo, L. Minale and F. Zollo, J. Nat. Prod., 1993, 56, 527–533,  DOI:10.1021/np50094a012.
698. L. Fiorini, M.-A. Tribalat, L. Sauvard, J. Cazareth, E. Lalli, I. Broutin, O. P. Thomas and I. Mus-Veteau, Oncotarget, 2015, 6, 22282–22297,  DOI:10.18632/oncotarget.4162.
699. A. D. Wright, H. Q. Wang, M. Gurrath, G. M. Konig, G. Kocak, G. Neumann, P. Loria, M. Foley and L. Tilley, J. Med. Chem., 2001, 44, 873–885,  DOI:10.1021/jm0010724.
700. R. M. Young, M. R. Adendorff, A. D. Wright and M. T. Davies-Coleman, Eur. J. Med. Chem., 2015, 93, 373–380,  DOI:10.1016/j.ejmech.2015.02.011.
701. L. Mayol, V. Piccialli and D. Sica, Tetrahedron Lett., 1985, 26, 1357–1360,  DOI:10.1016/S0040-4039(00)94893-7.
702. M. E. Rateb, W. E. Houssen, M. Schumacher, W. T. A. Harrison, M. Diederich, R. Ebel and M. Jaspars, J. Nat. Prod., 2009, 72, 1471–1476,  DOI:10.1021/np900233c.
703. J. S. Buckleton, P. R. Bergquist, R. C. Cambie, G. R. Clark, P. Karuso and C. E. F. Rickard, Acta Crystallogr., Sect. C: Struct. Chem., 1987, 43, 2430–2432,  DOI:10.1107/s0108270187087523.
704. J. A. Sánchez, A. Alfonso, M. Leirós, E. Alonso, M. E. Rateb, M. Jaspars, W. E. Houssen, R. Ebel and L. M. Botana, Cell. Physiol. Biochem., 2015, 37, 779–792,  DOI:10.1159/000430395.
705. Y. Murakami, Y. Oshima and T. Yasumoto, Nippon Suisan Gakkaishi, 1982, 48, 69–72,  DOI:10.2331/suisan.48.69.
706. H. Ehara, M. Makino, K. Kodama, K. Konoki, T. Ito, S.-i. Sekine, S. Fukuzawa, S. Yokoyama and K. Tachibana, ChemBioChem, 2015, 16, 1435–1439,  DOI:10.1002/cbic.201500141.
707. M. Puyana, J. Pawlik, J. Blum and W. Fenical, Rev. Bras. Farmacogn., 2015, 25, 592–599,  DOI:10.1016/j.bjp.2015.08.002.
708. A. Martinez, C. Duque, N. Hara and Y. Fujimoto, Nat. Prod. Lett., 1995, 6, 281–284,  DOI:10.1080/10575639508043171.
709. A. Martinez, C. Duque, N. Sato and Y. Fujimoto, Chem. Pharm. Bull., 1997, 45, 181–184,  DOI:10.1248/cpb.45.181.
710. J. Quintana, J. Brango-Vanegas, G. M. Costa, L. Castellanos, C. Arévalo and C. Duque, Rev. Bras. Farmacogn., 2015, 25, 199–207,  DOI:10.1016/j.bjp.2015.03.013.
711. S. M. Ribeiro and R. C. Pereira, Biochem. Syst. Ecol., 2015, 60, 211–214,  DOI:10.1016/j.bse.2015.04.020.
712. J. L. Keffer, A. Plaza and C. A. Bewley, Org. Lett., 2009, 11, 1087–1090,  DOI:10.1021/ol802890b.
713. C. E. Salomon, D. H. Williams and D. J. Faulkner, J. Nat. Prod., 1995, 58, 1463–1466,  DOI:10.1021/np50123a021.
714. V. D. Kadam and G. Sudhakar, Tetrahedron, 2015, 71, 1058–1067,  DOI:10.1016/j.tet.2014.12.092.
715. A. Cutignano and G. Nuzzo, Angew. Chem., Int. Ed., 2013, 52, 9256–9260,  DOI:10.1002/anie.201303039.
716. B. Seetharamsingh, P. R. Rajamohanan and D. Srinivasa Reddy, Org. Lett., 2015, 17, 1652–1655,  DOI:10.1021/acs.orglett.5b00345.
717. S. Das, T. K. Kuilya and R. K. Goswami, J. Org. Chem., 2015, 80, 6467–6489,  DOI:10.1021/acs.joc.5b00972.
718. S. Aoki, K. Higuchi, A. Kato, N. Murakami and M. Kobayashi, Tetrahedron, 1999, 55, 14865–14870,  DOI:10.1016/s0040-4020(99)00970-9.
719. J. Zhang, C. Li, L. Sun, G. Yu and H. Guan, Eur. J. Org. Chem., 2015, 2015, 4246–4253,  DOI:10.1002/ejoc.201500471.
720. Y. Nakao, T. Uehara, S. Matsunaga and N. Fusetani, J. Nat. Prod., 2002, 65, 922–924,  DOI:10.1021/np0106642.
721. S. Nickel, R. A. Serwa, F. Kaschani, S. Ninck, S. Zweerink, E. W. Tate and M. Kaiser, Chem.–Eur. J., 2015, 21, 10721–10728,  DOI:10.1002/chem.201500934.
722. H. Kim, J. Chin, H. Choi, K. Baek, T. G. Lee, S. E. Park, W. H. Wang, D. Hahn, I. Yang, J. Lee, B. Mun, M. Ekins, S. J. Nam and H. Kang, Org. Lett., 2013, 15, 5614,  DOI:10.1021/ol402803k.
723. H. Kim, J. Chin, H. Choi, K. Baek, T. G. Lee, S. E. Park, W. Wang, D. Hahn, I. Yang, J. Lee, B. Mun, M. Ekins, S. J. Nam and H. Kang, Org. Lett., 2013, 15, 100–103,  DOI:10.1021/ol3031318.
724. H. Kim, K.-J. Kim, J.-T. Yeon, S. H. Kim, D. H. Won, H. Choi, S.-J. Nam, Y.-J. Son and H. Kang, Mar. Drugs, 2014, 12, 2054–2065,  DOI:10.3390/md12042054.
725. D. J. Galler and K. A. Parker, Org. Lett., 2015, 17, 5544–5546,  DOI:10.1021/acs.orglett.5b02642.
726. D. M. Kushlan and D. J. Faulkner, J. Nat. Prod., 1991, 54, 1451–1454,  DOI:10.1021/np50077a043.
727. Z.-J. Xu, D.-X. Tan and Y. Wu, Org. Lett., 2015, 17, 5092–5095,  DOI:10.1021/acs.orglett.5b02599.
728. L. Carletti, G. Massiot and C. Debitus, WO20110513880 A1, 2011.
729. S. Specklin, G. Boissonnat, C. Lecourt, G. Sorin, M.-I. Lannou, J. Ardisson, F. Sautel, G. Massiot, C. Meyer and J. Cossy, Org. Lett., 2015, 17, 2446–2449,  DOI:10.1021/acs.orglett.5b00955.
730. R. Ueoka, Y. Nakao, S. Kawatsu, J. Yaegashi, Y. Matsumoto, S. Matsunaga and K. Furihata, J. Org. Chem., 2009, 74, 4203–4207,  DOI:10.1021/jo900380f.
731. M. D. Norris, M. V. Perkins and E. J. Sorensen, Org. Lett., 2015, 17, 668–671,  DOI:10.1021/ol503695j.
732. S. J. Piao, Y. L. Song, W. H. Jiao, F. Yang, X. F. Liu, W. S. Chen, B. N. Han and H. W. Lin, Org. Lett., 2013, 15, 3526–3529,  DOI:10.1021/ol400933x.
733. S. A. Ruider, T. Sandmeier and E. M. Carreira, Angew. Chem., Int. Ed., 2015, 54, 2378–2382,  DOI:10.1002/anie.201410419.
734. P. Crews and Y. Kakou, J. Am. Chem. Soc., 1988, 110, 4365–4368,  DOI:10.1021/ja00221a042.
735. R. N. Sonnenschein, T. A. Johnson, K. Tenney, F. A. Valeriote and P. Crews, J. Nat. Prod., 2006, 69, 145–147,  DOI:10.1021/np0503597.
736. L. Wang and K. J. Hale, Org. Lett., 2015, 17, 4200–4203,  DOI:10.1021/acs.orglett.5b01966.
737. P. S. Parameswaran, C. G. Naik, S. Y. Kamat and B. N. Pramanik, Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 1998, 37, 1258–1263.
738. M. Yokoya, K. Kobayashi, M. Sato and N. Saito, Mar. Drugs, 2015, 13, 4915–4933,  DOI:10.3390/md13084915.
739. W. D. Clark, T. Corbett, F. Valeriote and P. Crews, J. Am. Chem. Soc., 1997, 119, 9285–9286,  DOI:10.1021/ja971638m.
740. D. W. Laird, D. V. LaBarbera, X. D. Feng, T. S. Bugni, M. K. Harper and C. M. Ireland, J. Nat. Prod., 2007, 70, 741–746,  DOI:10.1021/np060489v.
741. B. K. Rubio, S. J. Robinson, C. E. Avalos and F. A. Valeriote, J. Nat. Prod., 2008, 71, 1475–1478,  DOI:10.1021/np800230d.
742. S. S. Curzon, J. M. Garcia and J. P. Konopelski, Tetrahedron Lett., 2015, 56, 2991–2994,  DOI:10.1016/j.tetlet.2014.09.087.
743. M. Arai, Y. Yamano, M. Fujita, A. Setiawan and M. Kobayashi, Bioorg. Med. Chem. Lett., 2012, 22, 1818–1821,  DOI:10.1016/j.bmcl.2011.10.023.
744. T. Huang, Y. Zou, M.-c. Wu, Q.-j. Zhao and H.-g. Hu, Chem. Nat. Compd., 2015, 51, 523–526,  DOI:10.1007/s10600-015-1329-1.
745. M. Kita, B. Gise, A. Kawamura and H. Kigoshi, Tetrahedron Lett., 2013, 54, 6826–6828,  DOI:10.1016/j.tetlet.2013.10.003.
746. T. Akindele, B. Gise, T. Sunaba, M. Kita and H. Kigoshi, Bull. Chem. Soc. Jpn., 2015, 88, 600–609,  DOI:10.1246/bcsj.20150003.
747. R. Ueoka, Y. Ise, S. Ohtsuka, S. Okada, T. Yamori and S. Matsunaga, J. Am. Chem. Soc., 2010, 132, 17692–17694,  DOI:10.1021/ja109275z.
748. T. Kuranaga, H. Mutoh, Y. Sesoko, T. Goto, S. Matsunaga and M. Inoue, J. Am. Chem. Soc., 2015, 137, 9443–9451,  DOI:10.1021/jacs.5b05550.
749. A. Bishara, A. Rudi, I. Goldberg, M. Aknin and Y. Kashman, Tetrahedron Lett., 2009, 50, 3820–3822,  DOI:10.1016/j.tetlet.2009.04.028.
750. K. Lehr, S. Schulthoff, Y. Ueda, R. Mariz, L. Leseurre, B. Gabor and A. Fürstner, Chem.–Eur. J., 2015, 21, 219–227,  DOI:10.1002/chem.201404873.
751. N. Fusetani, K. Yasumuro, S. Matsunaga and K. Hashimoto, Tetrahedron Lett., 1989, 30, 2809–2812,  DOI:10.1016/s0040-4039(00)99131-7.
752. M. Kita, H. Oka, A. Usui, T. Ishitsuka, Y. Mogi, H. Watanabe, M. Tsunoda and H. Kigoshi, Angew. Chem., Int. Ed., 2015, 54, 14174–14178,  DOI:10.1002/anie.201507795.
753. D. S. Dalisay, B. I. Morinaka, C. K. Skepper and T. F. Molinski, J. Am. Chem. Soc., 2009, 131, 7552,  DOI:10.1021/ja9024929.
754. Q. Xiao, K. Young and A. Zakarian, J. Am. Chem. Soc., 2015, 137, 5907–5910,  DOI:10.1021/jacs.5b03531.
755. T. Nishi, T. Kubota, J. Fromont, T. Sasaki and J. Kobayashi, Tetrahedron, 2008, 64, 3127–3132,  DOI:10.1016/j.tet.2008.01.111.
756. S. G. Davies, A. M. Fletcher, R. S. Shah, P. M. Roberts and J. E. Thomson, J. Org. Chem., 2015, 80, 4017–4029,  DOI:10.1021/acs.joc.5b00376.
757. Y. J. Lee, D. G. Lee, H. S. Rho, V. B. Krasokhin, H. J. Shin, J. S. Lee and H. S. Lee, J. Heterocycl. Chem., 2013, 50, 1400–1404,  DOI:10.1002/jhet.1599.
758. S. Hun Kim and J. Sperry, Tetrahedron Lett., 2015, 56, 5914–5915,  DOI:10.1016/j.tetlet.2015.09.033.
759. A. E. Wright, S. A. Pomponi, S. S. Cross and P. McCarthy, J. Org. Chem., 1992, 57, 4772–4775,  DOI:10.1021/jo00043a045.
760. F. Zhang, B. Wang, P. Prasad, R. J. Capon and Y. Jia, Org. Lett., 2015, 17, 1529–1532,  DOI:10.1021/acs.orglett.5b00327.
761. J. J. Jackson, H. Kobayashi, S. D. Steffens and A. Zakarian, Angew. Chem., Int. Ed., 2015, 54, 9971–9975,  DOI:10.1002/anie.201504113.
762. M. Tsuda, Y. Takahashi, J. Fromont, Y. Mikami and J. Kobayashi, J. Nat. Prod., 2005, 68, 1277–1278,  DOI:10.1021/np050076e.
763. E. M. Boyd and J. Sperry, Org. Lett., 2015, 17, 1344–1346,  DOI:10.1021/acs.orglett.5b00300.
764. A. D. Patil, N. V. Kumar, W. C. Kokke, M. F. Bean, A. J. Freyer, C. Debrosse, S. Mai, A. Truneh, D. J. Faulkner, B. Carte and A. L. Breen, J. Org. Chem., 1995, 60, 1182–1188,  DOI:10.1021/jo00110a021.
765. B. T. Parr, C. Economou and S. B. Herzon, Nature, 2015, 525, 507–510,  DOI:10.1038/nature14902.
766. I. B. Seiple, S. Su, I. S. Young, C. A. Lewis, J. Yamaguchi and P. S. Baran, Angew. Chem., Int. Ed., 2010, 49, 1095–1098,  DOI:10.1002/anie.200907112.
767. K. Namba, K. Takeuchi, Y. Kaihara, M. Oda, A. Nakayama, A. Nakayama, M. Yoshida and K. Tanino, Nat. Commun., 2015, 6, 8731,  DOI:10.1038/ncomms9731.
768. M. S. Buchanan, A. R. Carroll, D. Wessling, M. Jobling, V. M. Avery, R. A. Davis, Y. J. Feng, Y. F. Xue and L. Oster, J. Med. Chem., 2008, 51, 3583–3587,  DOI:10.1021/jm800314b.
769. S. J. Conn, S. M. Vreeland, A. N. Wexler, R. N. Pouwer, R. J. Quinn and S. Chamberland, J. Nat. Prod., 2015, 78, 120–124,  DOI:10.1021/np500772u.
770. L.-W. Tian, Y. Feng, Y. Shimizu, T. Pfeifer, C. Wellington, J. N. A. Hooper and R. J. Quinn, J. Nat. Prod., 2014, 77, 1210–1214,  DOI:10.1021/np500119e.
771. H. Gan, Y. Huang, W. Feng, W. Zhu and K. Guo, J. Chem. Res., 2015, 39, 336–339,  DOI:10.3184/174751915x14326563172262.
772. R. S. Compagnone, R. Avila, A. I. Suarez, O. V. Abrams, H. R. Rangel, F. Arvelo, I. C. Pina and E. Merentes, J. Nat. Prod., 1999, 62, 1443–1444,  DOI:10.1021/np9901938.
773. P. Das and A. T. Hamme II, Eur. J. Org. Chem., 2015, 2015, 5159–5166,  DOI:10.1002/ejoc.201500603.
774. E. Zubia, M. Ortega, J. L. Carballo and J. Salva, Tetrahedron, 1994, 50, 8153–8160,  DOI:10.1016/s0040-4020(01)85297-2.
775. L. Yeung, L. I. Pilkington, M. M. Cadelis, B. R. Copp and D. Barker, Beilstein J. Org. Chem., 2015, 11, 1991–1996,  DOI:10.3762/bjoc.11.215.
776. H. Nakamura, S. Deng, J. Kobayashi, Y. Ohizumi and Y. Hirata, Tetrahedron, 1986, 42, 4197–4201,  DOI:10.1016/S0040-4020(01)87643-2.
777. D. M. Kushlan and D. J. Faulkner, Tetrahedron, 1989, 45, 3307–3312,  DOI:10.1016/s0040-4020(01)81009-7.
778. Y. Sumii, N. Kotoku, A. Fukuda, T. Kawachi, Y. Sumii, M. Arai and M. Kobayashi, Bioorg. Med. Chem., 2015, 23, 966–975,  DOI:10.1016/j.bmc.2015.01.021.
779. Y. Sumii, N. Kotoku, A. Fukuda, T. Kawachi, M. Arai and M. Kobayashi, Mar. Drugs, 2015, 13, 7419–7432,  DOI:10.3390/md13127074.
780. P. L. Winder, H. L. Baker, P. Linley, E. A. Guzman, S. A. Pomponi, M. C. Diaz, J. K. Reed and A. E. Wright, Bioorg. Med. Chem., 2011, 19, 6599–6603,  DOI:10.1016/j.bmc.2011.09.026.
781. I. Chayboun, E. Boulifa, A. Ibn Mansour, F. Rodriguez-Serrano, E. Carrasco, P. Juan Alvarez, R. Chahboun and E. Alvarez-Manzaneda, J. Nat. Prod., 2015, 78, 1026–1036,  DOI:10.1021/np500975b.
782. B. Sullivan, P. Djura, D. E. McIntyre and D. J. Faulkner, Tetrahedron, 1981, 37, 979–982,  DOI:10.1016/s0040-4020(01)97672-0.
783. F. Marion, D. E. Williams, B. O. Patrick, I. Hollander, R. Mallon, S. C. Kim, D. M. Roll, L. Feldberg and R. J. Andersen, Org. Lett., 2006, 8, 321–324,  DOI:10.1021/ol052744t.
784. A. W. Markwell-Heys, K. K. W. Kuan and J. H. George, Org. Lett., 2015, 17, 4228–4231,  DOI:10.1021/acs.orglett.5b01973.
785. T. A. Johnson, T. Amagata, K. V. Sashidhara, A. G. Oliver, K. Tenney, T. Matainaho, K. K. H. Ang, J. H. McKerrow and P. Crews, Org. Lett., 2009, 11, 1975–1978,  DOI:10.1021/ol900446d.
786. G. Cimino, Tetrahedron Lett., 1975, 3723–3726,  DOI:10.1016/s0040-4039(00)91319-4.
787. C. Bürki, J. Bonjoch, B. Bradshaw, G. Villa and P. Renaud, Chem.–Eur. J., 2015, 21, 395–401,  DOI:10.1002/chem.201404766.
788. L. Mayol, V. Piccialli and D. Sica, Tetrahedron Lett., 1987, 28, 3601–3604,  DOI:10.1016/s0040-4039(00)95546-1.
789. N. L. Harvey, J. Krysiak, S. Chamni, S. W. Cho, S. A. Sieber and D. Romo, Chem.–Eur. J., 2015, 21, 1425–1428,  DOI:10.1002/chem.201405980.
790. K. D. Wellington, R. C. Cambie, P. S. Rutledge and P. R. Bergquist, J. Nat. Prod., 2000, 63, 79–85,  DOI:10.1021/np9903494.
791. T. P. Blaisdell and J. P. Morken, J. Am. Chem. Soc., 2015, 137, 8712–8715,  DOI:10.1021/jacs.5b05477.
792. A. Patra, C. W. J. Chang and P. J. Scheuer, J. Am. Chem. Soc., 1984, 106, 7981–7983,  DOI:10.1021/ja00337a061.
793. M. E. Daub, J. Prudhomme, K. L. Roch and C. D. Vanderwal, J. Am. Chem. Soc., 2015, 137, 4912–4915,  DOI:10.1021/jacs.5b01152.
794. R. P. Walker and D. J. Faulkner, J. Org. Chem., 1981, 46, 1098–1102,  DOI:10.1021/jo00319a012.
795. M. Nishizawa, H. Yamada and Y. Hayashi, Tetrahedron Lett., 1986, 27, 187–190,  DOI:10.1016/s0040-4039(00)83973-8.
796. S. Serra and V. Lissoni, Eur. J. Org. Chem., 2015, 2015, 2226–2234,  DOI:10.1002/ejoc.201403610.
797. W. Wang, B. Mun, Y. Lee, M. V. Reddy, Y. Park, J. Lee, H. Kim, D. Hahn, J. Chin, M. Ekins, S. J. Nam and H. Kang, J. Nat. Prod., 2013, 76, 170–177,  DOI:10.1021/np300573m.
798. J. G. Hubert, D. P. Furkert and M. A. Brimble, J. Org. Chem., 2015, 80, 2231–2239,  DOI:10.1021/jo502748s.
799. M. S. Butler and R. J. Capon, Aust. J. Chem., 1992, 45, 1705–1743,  DOI:10.1071/CH9921705.
800. A. Urosa, I. S. Marcos, D. Díez, J. M. Padrón and P. Basabe, J. Org. Chem., 2015, 80, 6447–6455,  DOI:10.1021/acs.joc.5b00876.
801. A. Urosa, I. S. Marcos, D. Díez, A. Lithgow, G. B. Plata, J. M. Padrón and P. Basabe, Mar. Drugs, 2015, 13, 2407–2423,  DOI:10.3390/md13042407.
802. D. T. A. Youssef, R. K. Yamaki, M. Kelly and P. J. Scheuer, J. Nat. Prod., 2002, 65, 2–6,  DOI:10.1021/np0101853.
803. Y. C. Chang, S. W. Tseng, L. L. Liu, Y. L. Chou, Y. S. Ho, M. C. Lu and J. H. Su, Mar. Drugs, 2012, 10, 987–997,  DOI:10.3390/md10050987.
804. M. Martín, A. Urosa, I. S. Marcos, D. Díez, J. M. Padrón and P. Basabe, J. Org. Chem., 2015, 80, 4566–4572,  DOI:10.1021/acs.joc.5b00420.
805. N. A. Eltahawy, A. K. Ibrahim, M. M. Radwan, S. A. Zaitone, M. Gomaa, M. A. ElSohly, H. A. Hassanean and S. A. Ahmed, Bioorg. Med. Chem. Lett., 2015, 25, 5819–5824,  DOI:10.1016/j.bmcl.2015.08.039.
806. F. Liu, S. Li, Z.-R. Ju, T.-T. Liu, R.-Y. Liang, X.-J. Liao and S.-H. Xu, J. Asian Nat. Prod. Res., 2015, 17, 851–855,  DOI:10.1080/10286020.2015.1009049.
807. Y.-B. Cheng, I.-W. Lo, L.-F. Shyur, C.-C. Yang, Y.-M. Hsu, J.-H. Su, M.-C. Lu, S.-F. Chiou, C.-C. Lan, Y.-C. Wu and F.-R. Chang, Tetrahedron, 2015, 71, 8601–8606,  DOI:10.1016/j.tet.2015.09.023.
808. C. B. Rao, D. C. Babu, T. V. Bharadwaj, D. Srikanth, K. S. Vardhan, T. V. Raju, R. A. Bunce and Y. Venkateswarlu, Nat. Prod. Res., 2015, 29, 70–76,  DOI:10.1080/14786419.2014.958742.
809. M. A. Ghandourah, W. M. Alarif, A. Abdel-Lateff, S. S. Al-Lihaibi, S.-E. N. Ayyad, S. A. Basaif and F. A. Badria, Med. Chem. Res., 2015, 24, 4070–4077,  DOI:10.1007/s00044-015-1456-z.
810. S.-Y. Cheng, S.-K. Wang, P.-W. Chen and C.-Y. Duh, Bioorg. Med. Chem. Lett., 2015, 25, 2353–2355,  DOI:10.1016/j.bmcl.2015.04.022.
811. N.-X. Zhang, X.-L. Tang, L. v. Ofwegen, L. Xue, W.-J. Song, P.-L. Li and G.-Q. Li, Chem. Biodiversity, 2015, 12, 273–283,  DOI:10.1002/cbdv.201400044.
812. W.-J. Lin, T.-Y. Wu, T.-R. Su, Z.-H. Wen, J.-J. Chen, L.-S. Fang, Y.-C. Wu and P.-J. Sung, Int. J. Mol. Sci., 2015, 16, 19508–19517,  DOI:10.3390/ijms160819508.
813. Q. Huang, W. Cheng, H. Long, H. Liu, L. v. Ofwegen and W. Lin, Helv. Chim. Acta, 2015, 98, 1202–1209,  DOI:10.1002/hlca.201500086.
814. A. Abdel-Lateff, W. M. Alarif, S.-E. N. Ayyad, S. S. Al-Lihaibi and S. A. Basaif, Nat. Prod. Res., 2015, 29, 24–30,  DOI:10.1080/14786419.2014.952637.
815. C.-S. Phan, S.-Y. Ng, E.-A. Kim, Y.-J. Jeon, K. Palaniveloo and C. Vairappan, Mar. Drugs, 2015, 13, 3103–3115,  DOI:10.3390/md13053103.
816. H.-M. Chung, W.-H. Wang, T.-L. Hwang, Y.-C. Wu and P.-J. Sung, Nat. Prod. Commun., 2015, 10, 835–843.
817. L. Yu, L. Lin, B. Long, Y. Chen, F. Lei, L. Wen, H. Sun, C. Gao and R. Huang, Helv. Chim. Acta, 2015, 98, 710–718,  DOI:10.1002/hlca.201400301.
818. C. N. Diep, E. G. Lyakhova, D. V. Berdyshev, A. I. Kalinovsky, Vu A. Tu, N. X. Cuong, N. H. Nam, C. V. Minh and V. A. Stonik, Tetrahedron Lett., 2015, 56, 7001–7004,  DOI:10.1016/j.tetlet.2015.10.102.
819. B.-W. Chen, C. Uvarani, C.-Y. Huang, T.-L. Hwang, C.-F. Dai and J.-H. Sheu, Bioorg. Med. Chem. Lett., 2015, 25, 92–95,  DOI:10.1016/j.bmcl.2014.11.002.
820. C.-H. Chao, T.-Z. Huang, C.-Y. Wu, B.-W. Chen, C.-Y. Huang, T.-L. Hwang, C.-F. Dai and J.-H. Sheu, RSC Adv., 2015, 5, 74256–74262,  10.1039/c5ra13436f.
821. T.-H. Hsiao, C.-H. Cheng, T.-Y. Wu, M.-C. Lu, W.-F. Chen, Z.-H. Wen, C.-F. Dai, Y.-C. Wu and P.-J. Sung, Molecules, 2015, 20, 13205–13215,  DOI:10.3390/molecules200713205.
822. T.-H. Hsiao, C.-S. Sung, Y.-H. Lan, Y.-C. Wang, M.-C. Lu, Z.-H. Wen, Y.-C. Wu and P.-J. Sung, Mar. Drugs, 2015, 13, 3443–3453,  DOI:10.3390/md13063443.
823. S.-Y. Cheng, S.-K. Wang, M.-K. Hsieh and C.-Y. Duh, Int. J. Mol. Sci., 2015, 16, 6140–6152,  DOI:10.3390/ijms16036140.
824. B. Yang, J. Huang, X. Lin, S. Liao, X. Zhou, J. Liu, J. Wang, L. Wang and Y. Liu, Helv. Chim. Acta, 2015, 98, 834–841,  DOI:10.1002/hlca.201400341.
825. X. Liu, J. Zhang, Q. Liu, G. Tang, H. Wang, C. Fan and S. Yin, Molecules, 2015, 20, 13324–13335,  DOI:10.3390/molecules200713324.
826. J.-Y. Zhu, W. Li, J.-M. Bao, J.-S. Zhang, S. Yin and G.-H. Tang, Biochem. Syst. Ecol., 2015, 62, 6–10,  DOI:10.1016/j.bse.2015.07.033.
827. K. O. Al-Footy, W. M. Alarif, F. Asiri, M. M. Aly and S.-E. N. Ayyad, Med. Chem. Res., 2015, 24, 505–512,  DOI:10.1007/s00044-014-1147-1.
828. K.-M. Liu, C.-H. Cheng, W.-F. Chen, M.-C. Lu, L.-S. Fang, Z.-H. Wen, J.-H. Su, Y.-C. Wu and P.-J. Sung, Nat. Prod. Commun., 2015, 10, 1163–1168.
829. T.-C. Tsai, H.-Y. Chen, J.-H. Sheu, M. Y. Chiang, Z.-H. Wen, C.-F. Dai and J.-H. Su, J. Agric. Food Chem., 2015, 63, 7211–7218,  DOI:10.1021/acs.jafc.5b01931.
830. L.-F. Liang, T. Kurtán, A. Mándi, L.-X. Gao, J. Li, W. Zhang and Y.-W. Guo, Eur. J. Org. Chem., 2014, 2014, 1841–1847,  DOI:10.1002/ejoc.201301683.
831. M. Gutierrez, T. L. Capson, C. M. Guzman, J. Gonzalez, E. Ortega-Barria, E. Quinoa and R. Riguera, J. Nat. Prod., 2005, 68, 614–616,  DOI:10.1021/np049745z.
832. A. Y. Ma and Z. W. Deng, J. Nat. Prod., 2008, 71, 1152–1160,  DOI:10.1021/np800003w.
833. F. J. Schmitz, D. J. Vanderah and L. S. Ciereszko, J. Chem. Soc., Chem. Commun., 1974, 407–408,  10.1039/c39740000407.
834. S.-S. Wang, Y.-B. Cheng, Y.-C. Lin, C.-C. Liaw, J.-Y. Chang, Y.-H. Kuo and Y.-C. Shen, Mar. Drugs, 2015, 13, 5796–5814,  DOI:10.3390/md13095796.
835. A. R. Diaz-Marrero, G. Porras and M. Cueto, Tetrahedron, 2009, 65, 6029–6033,  DOI:10.1016/j.tet.2009.05.068.
836. C.-T. Yin, Z.-H. Wen, Y.-H. Lan, Y.-C. Chang, Y.-C. Wu and P.-J. Sung, Chem. Pharm. Bull., 2015, 63, 752–756,  DOI:10.1248/cpb.c15-00414.
837. M. L. Qin, X. M. Li and B. G. Wang, Chin. J. Chem., 2012, 30, 1278–1282,  DOI:10.1002/cjoc.201200145.
838. A. F. Ahmed, R. Shiue, G. Wang, C. Dai, Y. Kuo and J. Sheu, Tetrahedron, 2003, 59, 7337–7344,  DOI:10.1016/s0040-4020(03)01138-4.
839. W.-F. Chen, C.-T. Yin, C.-H. Cheng, M.-C. Lu, L.-S. Fang, W.-H. Wang, Z.-H. Wen, J.-J. Chen, Y.-C. Wu and P.-J. Sung, Int. J. Mol. Sci., 2015, 16, 3298–3306,  DOI:10.3390/ijms16023298.
840. W.-T. Chen, J. Li, J.-R. Wang, X.-W. Li and Y.-W. Guo, RSC Adv., 2015, 5, 23973–23980,  10.1039/c5ra01151e.
841. C. Y. Duh, S. K. Wang, H. K. Tseng, J. H. Sheu and M. Y. Chiang, J. Nat. Prod., 1998, 61, 844–847,  DOI:10.1021/np980021v.
842. C.-Y. Huang, P.-J. Sung, C. Uvarani, J.-H. Su, M.-C. Lu, T.-L. Hwang, C.-F. Dai, S.-L. Wu and J.-H. Sheu, Sci. Rep., 2015, 5, 15624,  DOI:10.1038/srep15624.
843. N. H. Nam, P. T. Tung, N. T. Ngoc, T. T. Hong Hanh, N. P. Thao, N. V. Thanh, N. X. Cuong, Do T. Thao, T. T. Huong, Do C. Thung, P. V. Kiem, Y. H. Kim and C. V. Minh, Chem. Pharm. Bull., 2015, 63, 636–640,  DOI:10.1248/cpb.c15-00273.
844. Y.-D. Su, T.-R. Su, Z.-H. Wen, T.-L. Hwang, L.-S. Fang, J.-J. Chen, Y.-C. Wu, J.-H. Sheu and P.-J. Sung, Mar. Drugs, 2015, 13, 1037–1050,  DOI:10.3390/md13021037.
845. Y.-D. Su, T.-Y. Wu, Z.-H. Wen, C.-C. Su, Y.-H. Chen, Y.-C. Chang, Y.-C. Wu, J.-H. Sheu and P.-J. Sung, Mar. Drugs, 2015, 13, 7138–7149,  DOI:10.3390/md13127060.
846. J.-F. Sun, B. Yang, X.-F. Zhou, X.-W. Yang, L. Wang and Y. Liu, Nat. Prod. Res., 2015, 29, 807–812,  DOI:10.1080/14786419.2014.987774.
847. K. Ueda, W. Maarisit, K. Yano, T. Miyazato, P. K. Roy and J. Taira, Heterocycles, 2015, 91, 505–514,  DOI:10.3987/COM-14-13149.
848. X.-W. Zhang, X.-L. Tang, H.-R. Yuan, D.-Q. Feng, P. Su, P.-L. Li and G.-Q. Li, Nat. Prod. Res., 2015, 29, 2018–2023,  DOI:10.1080/14786419.2015.1027893.
849. T.-Z. Huang, B.-W. Chen, C.-Y. Huang, T.-L. Hwang, C. Uvarani, C.-F. Dai, P.-J. Sung, J.-H. Su and J.-H. Sheu, Mar. Drugs, 2015, 13, 2757–2769,  DOI:10.3390/md13052757.
850. J. Zhang, L.-L. Liu, B.-L. Zhong, X.-J. Liao and S.-H. Xu, Steroids, 2015, 98, 100–106,  DOI:10.1016/j.steroids.2015.03.004.
851. X.-P. Sun, F. Cao, C.-L. Shao, M. Wang, X.-L. Zhang and C.-Y. Wang, Chem. Biodiversity, 2015, 12, 1068–1074,  DOI:10.1002/cbdv.201400217.
852. A. M. Elbagory, M. Meyer, A.-H. A. M. Ali, F. Ameer, S. Parker-Nance, M. T. Benito, E. G. Doyagüez, M. Luisa Jimeno and A. A. Hussein, Steroids, 2015, 101, 110–115,  DOI:10.1016/j.steroids.2015.06.009.
853. C.-R. Tsai, C.-Y. Huang, B.-W. Chen, Y.-Y. Tsai, S.-P. Shih, T.-L. Hwang, C.-F. Dai, S.-Y. Wang and J.-H. Sheu, RSC Adv., 2015, 5, 12546–12554,  10.1039/C4RA13977A.
854. Vu A. Tu, E. G. Lyakhova, C. N. Diep, A. I. Kalinovsky, P. S. Dmitrenok, N. X. Cuong, N. V. Thanh, E. S. Menchinskaya, E. A. Pislyagin, N. H. Nam, P. V. Kiem, V. A. Stonik and C. V. Minh, Steroids, 2015, 104, 246–251,  DOI:10.1016/j.steroids.2015.10.010.
855. F. Cao, H.-Y. Liu, J. Zhao, Y.-C. Fang and C.-Y. Wang, Nat. Prod. Res., 2015, 29, 169–173,  DOI:10.1080/14786419.2014.971321.
856. K. H. Shaker, M. Göhl, T. Müller and K. Seifert, Chem. Biodiversity, 2015, 12, 1746–1755,  DOI:10.1002/cbdv.201400406.
857. I. Gladkikh, M. Monastyrnaya, E. Zelepuga, O. Sintsova, V. Tabakmakher, O. Gnedenko, A. Ivanov, K.-F. Hua and E. Kozlovskaya, Mar. Drugs, 2015, 13, 6038–6063,  DOI:10.3390/md13106038.
858. Y. Subburaj, U. Ros, E. Hermann, R. Tong and A. J. García-Sáez, J. Biol. Chem., 2015, 290, 4856–4865,  DOI:10.1074/jbc.m114.600676.
859. M. Pennington, S. Chang, S. Chauhan, R. Huq, R. Tajhya, S. Chhabra, R. Norton and C. Beeton, Mar. Drugs, 2015, 13, 529–542,  DOI:10.3390/md13010529.
860. S. C. Chang, R. Huq, S. Chhabra, C. Beeton, M. W. Pennington, B. J. Smith and R. S. Norton, FEBS J., 2015, 282, 2247–2259,  DOI:10.1111/febs.13294.
861. M. Jouiaei, K. Sunagar, A. Federman Gross, H. Scheib, P. F. Alewood, Y. Moran and B. G. Fry, Mol. Biol. Evol., 2015, 32, 1598–1610,  DOI:10.1093/molbev/msv050.
862. M. Alam and P. Sharama, J. Org. Chem., 1989, 54, 1896–1900,  DOI:10.1021/jo00269a027.
863. D. Friedrich and L. A. Paquette, J. Nat. Prod., 2002, 65, 126–130,  DOI:10.1021/np0103822.
864. J. Stephen Clark, L. Delion and L. J. Farrugia, Chem.–Eur. J., 2015, 21, 4772–4780,  DOI:10.1002/chem.201406051.
865. M. Ochi, K. yamada, K. Futatsugi, H. Kotsuki and K. Shibata, Chem. Lett., 1990, 2183–2186,  DOI:10.1246/cl.1990.2183.
866. A. D. Rodriguez, J. J. Soto and I. C. Pina, J. Nat. Prod., 1995, 58, 1209–1216,  DOI:10.1021/np50122a008.
867. A. D. Rodriguez, J. J. Soto and C. L. Barnes, J. Org. Chem., 2000, 65, 7700–7702,  DOI:10.1021/jo000996w.
868. L. Zhu and R. Tong, Org. Lett., 2015, 17, 1966–1969,  DOI:10.1021/acs.orglett.5b00700.
869. L. Zhu, Y. Liu, R. Ma and R. Tong, Angew. Chem., Int. Ed., 2015, 54, 627–632,  DOI:10.1002/anie.201409618.
870. Y. Seo, K. W. Cho, J. Rho, J. Shin, B. Kwon, S. Bok and J. Song, Tetrahedron, 1996, 52, 10583,  DOI:10.1016/0040-4020(96)00606-0.
871. N. C. Eichenauer, R. Tschersich and J. Pietruszka, J. Nat. Prod., 2015, 78, 2782–2790,  DOI:10.1021/acs.jnatprod.5b00757.
872. J. H. Sheu, K. C. Hung, G. H. Wang and C. Y. Duh, J. Nat. Prod., 2000, 63, 1603–1607,  DOI:10.1021/np000271n.
873. M. Kousara, A. Ferry, F. Le Bideau, K. L. Serré, I. Chataigner, E. Morvan, J. Dubois, M. Chéron and F. Dumas, Chem. Commun., 2015, 51, 3458–3461,  10.1039/c4cc10041g.
874. C. M. Miller, T. Benneche and M. A. Tius, Org. Biomol. Chem., 2015, 13, 4051–4058,  10.1039/c5ob00074b.
875. K. Iguchi, M. Iwashima and K. Watanabe, J. Nat. Prod., 1995, 58, 790–793,  DOI:10.1021/np50119a025.
876. M. Lorentzen, A. Bayer, M. O. Sydnes and K. B. Jørgensen, Tetrahedron, 2015, 71, 8278–8284,  DOI:10.1016/j.tet.2015.09.003.
877. R. Sakai and T. Higa, Chem. Lett., 1987, 127–128,  DOI:10.1246/cl.1987.127.
878. M. Tadesse, V. Torfoss, M. B. Strom, E. Hansen, J. H. Andersen, K. Stensvag and T. Haug, Biochem. Syst. Ecol., 2010, 38, 827–829,  DOI:10.1016/j.bse.2010.04.002.
879. A. N. Pearce, E. W. Chia, M. V. Berridge, E. W. Maas, M. J. Page, J. L. Harper, V. L. Webb and B. R. Copp, Tetrahedron, 2008, 64, 5748–5755,  DOI:10.1016/j.tet.2008.04.012.
880. S. K. Pandey, Y. Guttormsen, B. E. Haug, C. Hedberg and A. Bayer, Org. Lett., 2015, 17, 122–125,  DOI:10.1021/ol503348n.
881. A. H. Khan and J. S. Chen, Org. Lett., 2015, 17, 3718–3721,  DOI:10.1021/acs.orglett.5b01702.
882. K. O. Hanssen, B. Schuler, A. J. Williams, T. B. Demissie, E. Hansen and J. H. Anderson, Angew. Chem., Int. Ed., 2012, 51, 12238–12241,  DOI:10.1002/anie.201203960.
883. Y. M. Díaz, G. V. Laverde, L. R. Gamba, H. M. Wandurraga, C. Arévalo-Ferro, F. R. Rodríguez, C. D. Beltrán and L. C. Hernández, Rev. Bras. Farmacogn., 2015, 25, 605–611,  DOI:10.1016/j.bjp.2015.08.007.
884. J. Taira, E. Tsuchida, M. Uehara, Y. Kinjyo, P. K. Roy and K. Ueda, Bioorg. Med. Chem. Lett., 2015, 25, 4496–4499,  DOI:10.1016/j.bmcl.2015.08.079.
885. N. P. Thao, B. T. Thuy Luyen, N. T. Thanh Ngan, L. D. Dat, N. X. Cuong, N. H. Nam, P. V. Kiem, S. B. Song, C. V. Minh and Y. H. Kim, Arch. Pharmacal Res., 2015, 38, 769–775,  DOI:10.1007/s12272-014-0382-9.
886. N. Thao, B. Luyen, R. Brun, M. Kaiser, P. Van Kiem, C. Van Minh, T. Schmidt, J. Kang and Y. Kim, Molecules, 2015, 20, 12459–12468,  DOI:10.3390/molecules200712459.
887. N. P. Thao, B. T. Thuy Luyen, S. H. Lee, H. D. Jang, P. V. Kiem, C. V. Minh and Y. H. Kim, Med. Chem. Res., 2015, 24, 3551–3560,  DOI:10.1007/s00044-015-1395-8.
888. Y.-J. Wu, C.-A. Neoh, C.-Y. Tsao, J.-H. Su and H.-H. Li, Int. J. Mol. Sci., 2015, 16, 16469–16482,  DOI:10.3390/ijms160716469.
889. E.-J. Kim, J.-I. Kang, J.-W. Kwak, C.-H. Jeon, N.-H. Tung, Y.-H. Kim, C.-H. Choi, J.-W. Hyun, Y.-S. Koh, E.-S. Yoo and H.-K. Kang, Mar. Drugs, 2015, 13, 1340–1359,  DOI:10.3390/md13031340.
890. Y.-Y. Lin, S.-C. Lin, C.-W. Feng, P.-C. Chen, Y.-D. Su, C.-M. Li, S.-N. Yang, Y.-H. Jean, P.-J. Sung, C.-Y. Duh and Z.-H. Wen, Mar. Drugs, 2015, 13, 2559–2579,  DOI:10.3390/md13052559.
891. S. S. Oigman, Y. F. d. Miranda Fernandes, D. Teles, L. F. Maia, R. d. A. Epifanio and C. M. Rezende, Rev. Bras. Farmacogn., 2015, 25, 612–618,  DOI:10.1016/j.bjp.2015.08.004.
892. T. S. Sousa, G. Nuzzo, M. C. M. Torres, N. P. Lopes, A. Cutignano, P. C. Jimenez, E. A. Santos, B. A. Gomes, A. Sardo, O. D. L. Pessoa, L. V. Costa-Lotufo and A. Fontana, Rev. Bras. Farmacogn., 2015, 25, 600–604,  DOI:10.1016/j.bjp.2015.08.010.
893. A. R. Carroll, S. J. Wild, S. Duffy and V. M. Avery, Tetrahedron Lett., 2012, 53, 2873–2875,  DOI:10.1016/j.tetlet.2012.03.126.
894. R. A. Davis, M. Sykes, V. M. Avery, D. Camp and R. J. Quinn, Bioorg. Med. Chem., 2011, 19, 6615–6619,  DOI:10.1016/j.bmc.2011.06.006.
895. Y. Dashti, M.-L. Vial, S. A. Wood, G. D. Mellick, C. Roullier and R. J. Quinn, Tetrahedron, 2015, 71, 7879–7884,  DOI:10.1016/j.tet.2015.08.017.
896. J. Wang, M. R. Prinsep, D. P. Gordon, M. J. Page and B. R. Copp, J. Nat. Prod., 2015, 78, 530–533,  DOI:10.1021/np500752y.
897. G. Sodano and A. Spinella, Tetrahedron Lett., 1986, 27, 2505–2508,  DOI:10.1016/s0040-4039(00)84569-4.
898. A. E. Trindade-Silva, G. E. Lim-Fong, K. H. Sharp and M. G. Haygood, Curr. Opin. Biotechnol., 2010, 21, 834–842,  DOI:10.1016/j.copbio.2010.09.018.
899. H.-B. Yu, F. Yang, Y.-Y. Li, J.-H. Gan, W.-H. Jiao and H.-W. Lin, J. Nat. Prod., 2015, 78, 1169–1173,  DOI:10.1021/acs.jnatprod.5b00081.
900. CAS Registry Number: 342403-17-2, A07.175.048, Aurora Screening Library, Aurora Fine Chemicals LLC, 20 Oct 2016.
901. CAS Registry Number: 342403-17-2, FCH2042888-1, FCH2042888, FCH Group Reagents for Synthesis, 17 Nov 2016.
902. J. S. Kim, S. S. Kang, K. H. Son, H. W. Chang, H. P. Kim and K. H. Bae, Saengyak Hakhoechi, 2002, 32, 105–109.
903. X.-R. Tian, H.-F. Tang, Y.-S. Li, H.-W. Lin, X.-Y. Zhang, J.-T. Feng and X. Zhang, Rec. Nat. Prod., 2015, 9, 628–632.
904. A. J. Blackman and R. D. Green, Aust. J. Chem., 1987, 40, 1655–1662,  DOI:10.1071/ch9871655.
905. A. R. Carroll, S. Duffy, M. Sykes and V. M. Avery, Org. Biomol. Chem., 2011, 9, 604–609,  10.1039/c0ob00538j.
906. S. Ahmad, S. Choudhury and F. A. Khan, Tetrahedron, 2015, 71, 4192–4202,  DOI:10.1016/j.tet.2015.04.091.
907. J. Kilcoyne, M. J. Twiner, P. McCarron, S. Crain, S. D. Giddings, B. Foley, F. Rise, P. Hess, A. L. Wilkins and C. O. Miles, J. Agric. Food Chem., 2015, 63, 5083–5091,  DOI:10.1021/acs.jafc.5b01320.
908. L. V. Hjørnevik, A. K. Frøyset, T. A. Grønset, K. Rungruangsak-Torrissen and K. E. Fladmark, Mar. Drugs, 2015, 13, 7390–7402,  DOI:10.3390/md13127072.
909. Y. Bourne, G. Sulzenbacher, Z. Radić, R. Aráoz, M. Reynaud, E. Benoit, A. Zakarian, D. Servent, J. Molgó, P. Taylor and P. Marchot, Structure, 2015, 23, 1106–1115,  DOI:10.1016/j.str.2015.04.009.
910. R. Aráoz, G. Ouanounou, B. I. Iorga, A. Goudet, D. Alili, M. Amar, E. Benoit, J. Molgó and D. Servent, Toxicol. Sci., 2015, 147, 156–167,  DOI:10.1093/toxsci/kfv119.
911. L. Salvitti, S. Wood, L. Winsor and S. Cary, Mar. Drugs, 2015, 13, 756–769,  DOI:10.3390/md13020756.
912. A. Cutignano, J. Moles, C. Avila and A. Fontana, J. Nat. Prod., 2015, 78, 1761–1764,  DOI:10.1021/acs.jnatprod.5b00378.
913. A. M. White, G. K. Pierens, T. Skinner-Adams, K. T. Andrews, P. V. Bernhardt, E. H. Krenske, E. Mollo and M. J. Garson, J. Nat. Prod., 2015, 78, 1422–1427,  DOI:10.1021/acs.jnatprod.5b00354.
914. I. Wayan Mudianta, A. M. White and M. J. Garson, Nat. Prod. Commun., 2015, 10, 865–873.
915. K. W. L. Yong, I. Wayan Mudianta, K. L. Cheney, E. Mollo, J. T. Blanchfield and M. J. Garson, J. Nat. Prod., 2015, 78, 421–430,  DOI:10.1021/np500797b.
916. A. Petraki, E. Ioannou, P. Papazafiri and V. Roussis, J. Nat. Prod., 2015, 78, 462–467,  DOI:10.1021/np500851w.
917. A. Kawamura, M. Kita and H. Kigoshi, Angew. Chem., Int. Ed., 2015, 54, 7073–7076,  DOI:10.1002/anie.201501749.
918. M. Gavagnin, E. Mollo and G. Cimino, Rev. Bras. Farmacogn., 2015, 25, 588–591,  DOI:10.1016/j.bjp.2015.07.028.
919. P. Sharma and J. E. Moses, Synlett, 2010, 525–528,  DOI:10.1055/s-0029-1218544.
920. D. Rudd, K. Benkendorff and N. H. Voelcker, Mar. Drugs, 2015, 13, 1410–1431,  DOI:10.3390/md13031410.
921. W. D. Raverty, R. H. Thomson and T. J. King, J. Chem. Soc., Perkin Trans. 1, 1977, 1204–1211,  10.1039/p19770001204.
922. K. Kondo, J. Nishi, M. Ishibahi and J. Kobayashi, J. Nat. Prod., 1994, 57, 1008–1011,  DOI:10.1021/np50109a023.
923. A. Aiello, F. Borrelli, R. Capasso, E. Fattorusso, P. Luciano and M. Menna, Bioorg. Med. Chem. Lett., 2003, 13, 4481–4483,  DOI:10.1016/j.bmcl.2003.08.081.
924. I. E. Kasheverov, I. V. Shelukhina, D. S. Kudryavtsev, T. N. Makarieva, E. N. Spirova, A. G. Guzii, V. A. Stonik and V. I. Tsetlin, Mar. Drugs, 2015, 13, 1255–1266,  DOI:10.3390/md13031255.
925. G. R. Pettit, T. H. Smith, P. M. Arce, E. J. Flahive, C. R. Anderson, J.-C. Chapuis, J.-P. Xu, T. L. Groy, P. E. Belcher and C. B. Macdonald, J. Nat. Prod., 2015, 78, 476–485,  DOI:10.1021/np500925y.
926. G. R. Pettit, J. Xu, F. Hogan, M. D. Williams, D. L. Doubek, J. M. Schmidt, R. L. Cerny and M. R. Boyd, J. Nat. Prod., 1997, 60, 752–754,  DOI:10.1021/np9700230.
927. Jayaseelan, B. Franklin and R. Pushpabai Rajesh, Toxicon, 2015, 103, 39–47,  DOI:10.1016/j.toxicon.2015.06.017.
928. R. Pushpabai Rajesh, J. Pept. Sci., 2015, 21, 29–39,  DOI:10.1002/psc.2715.
929. M. Zhou, L. Wang, Y. Wu, J. Liu, D. Sun, X. Zhu, Y. Feng, M. Qin, S. Chen and A. Xu, Toxicon, 2015, 98, 5–11,  DOI:10.1016/j.toxicon.2015.01.009.
930. S. Wang, C. Zhao, Z. Liu, X. Wang, N. Liu, W. Du and Q. Dai, Mar. Drugs, 2015, 13, 3259–3275,  DOI:10.3390/md13063259.
931. V. Lavergne, I. Harliwong, A. Jones, D. Miller, R. J. Taft and P. F. Alewood, Proc. Natl. Acad. Sci. U. S. A., 2015, 112, E3782–E3791,  DOI:10.1073/pnas.1501334112.
932. J. L. B. Neves, Z. Lin, J. S. Imperial, A. Antunes, V. Vasconcelos, B. M. Olivera and E. W. Schmidt, Org. Lett., 2015, 17, 4933–4935,  DOI:10.1021/acs.orglett.5b02389.
933. H. Safavi-Hemami, J. Gajewiak, S. Karanth, S. D. Robinson, B. Ueberheide, A. D. Douglass, A. Schlegel, J. S. Imperial, M. Watkins, P. K. Bandyopadhyay, M. Yandell, Q. Li, A. W. Purcell, R. S. Norton, L. Ellgaard and B. M. Olivera, Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 1743–1748,  DOI:10.1073/pnas.1423857112.
934. S. T. S. Chan, M. A. Pullar, I. M. Khalil, E. Allouche, D. Barker and B. R. Copp, Tetrahedron Lett., 2015, 56, 1486–1488,  DOI:10.1016/j.tetlet.2015.02.024.
935. T. Won, C.-K. Kim, S.-H. Lee, B. Rho, S. Lee, D.-C. Oh, K.-B. Oh and J. Shin, Mar. Drugs, 2015, 13, 3836–3848,  DOI:10.3390/md13063836.
936. D. Hahn, G. Jin Kim, H. Choi and H. Kang, Nat. Prod. Sci., 2015, 21, 278–281,  DOI:10.20307/nps.2015.21.4.278.
937. T. Tran, N. Pham, M. Ekins, J. Hooper and R. Quinn, Mar. Drugs, 2015, 13, 4556–4575,  DOI:10.3390/md13074556.
938. D. T. A. Youssef, G. A. Mohamed, L. A. Shaala, J. M. Badr, F. H. Bamanie and S. R. M. Ibrahim, Phytochem. Lett., 2015, 13, 212–217,  DOI:10.1016/j.phytol.2015.06.012.
939. N. K. Utkina, Nat. Prod. Commun., 2015, 10, 1547–1555.
940. S. T. S. Chan, P. R. Patel, T. R. Ransom, C. J. Henrich, T. C. McKee, A. K. L. Goey, K. M. Cook, W. D. Figg, J. B. McMahon, M. J. Schnermann and K. R. Gustafson, J. Am. Chem. Soc., 2015, 137, 5569–5575,  DOI:10.1021/jacs.5b02156.
941. N. Oku, S. Matsunaga and N. Fusetani, J. Am. Chem. Soc., 2003, 125, 2044–2045,  DOI:10.1021/ja0296780.
942. K. C. Nicolaou, Z. Lu, R. Li, J. R. Woods and T.-i. Sohn, J. Am. Chem. Soc., 2015, 137, 8716–8719,  DOI:10.1021/jacs.5b05575.
943. J. A. Tincu and S. W. Taylor, J. Nat. Prod., 2002, 65, 377–378,  DOI:10.1021/np010352z.
944. M. A. Pullar, D. Barker and B. R. Copp, Tetrahedron Lett., 2015, 56, 5604–5606,  DOI:10.1016/j.tetlet.2015.08.047.
945. S. M. Verbitski, C. L. Mayne, R. A. Davis, G. P. Concepcion and C. M. Ireland, J. Org. Chem., 2002, 67, 7124–7126,  DOI:10.1021/jo026012f.
946. B. M. Trost, M. Osipov, S. Krüger and Y. Zhang, Chem. Sci., 2015, 6, 349–353,  10.1039/c4sc01826e.
947. R. Pushpabai Rajesh and M. Annappan, Anticancer Res., 2015, 35, 283–376.
948. J. Kobayashi, G. C. Harbour, J. Gilmore and K. L. Rinehart, J. Am. Chem. Soc., 1984, 106, 1526–1528,  DOI:10.1021/ja00317a080.
949. D. M. Tapiolas, B. F. Bowden, E. Abou-Mansour, R. H. Willis, J. R. Doyle, A. N. Muirhead, C. Liptrot, L. E. Llewellyn and C. W. Wolff, J. Nat. Prod., 2009, 72, 1115–1120,  DOI:10.1021/np900099j.
950. M. S. Liberio, M. C. Sadowski, R. A. Davis, A. Rockstroh, R. Vasireddy, M. L. Lehman and C. C. Nelson, Oncotarget, 2015, 6, 43944–43963,  DOI:10.18632/oncotarget.6267.
951. I. H. Lee, C. Q. Zhao, Y. Cho, S. S. L. Harwig, E. L. Cooper and R. I. Lehrer, FEBS Lett., 1997, 400, 158–162,  DOI:10.1016/S0014-5793(96)01374-9.
952. O. N. Silva, I. C. M. Fensterseifer, E. A. Rodrigues, H. H. S. Holanda, N. R. F. Novaes, J. P. A. Cunha, T. M. B. Rezende, K. G. Magalhães, S. E. Moreno, M. S. Jerônimo, A. L. Bocca and O. L. Franco, Antimicrob. Agents Chemother., 2015, 59, 1620–1626,  DOI:10.1128/aac.03732-14.
953. R. Dossi, R. Frapolli, S. Di Giandomenico, L. Paracchini, F. Bozzi, S. Brich, V. Castiglioni, P. Borsotti, D. Belotti, S. Uboldi, R. Sanfilippo, E. Erba, R. Giavazzi, S. Marchini, S. Pilotti, M. D'Incalci and G. Taraboletti, Int. J. Cancer, 2015, 136, 721–730,  DOI:10.1002/ijc.29023.
954. M. B. Potts, E. A. McMillan, T. I. Rosales, H. Seok Kim, Y.-H. Ou, J. E. Toombs, R. A. Brekken, M. D. Minden, J. B. MacMillan and M. A. White, Nat. Chem. Biol., 2015, 11, 401–408,  DOI:10.1038/nchembio.1797.
955. R. A. Davis, W. Aalbersberg, S. Meo, R. M. da Rocha and C. M. Ireland, Tetrahedron, 2002, 58, 3263–3269,  DOI:10.1016/s0040-4020(02)00228-4.
956. M. K. Thorson, R. M. Van Wagoner, M. Kay Harper, C. M. Ireland, T. Majtan, J. P. Kraus and A. M. Barrios, Bioorg. Med. Chem. Lett., 2015, 25, 1064–1066,  DOI:10.1016/j.bmcl.2015.01.013.
957. A. Aiello, E. Fattorusso, P. Luciano, A. Macho, M. Menna and E. Munoz, J. Med. Chem., 2005, 48, 3410–3416,  DOI:10.1021/jm0489915.
958. J. L. Harper, I. M. Khalil, L. Shaw, M.-L. Bourguet-Kondracki, J. Dubois, A. Valentin, D. Barker and B. R. Copp, Mar. Drugs, 2015, 13, 5102–5110,  DOI:10.3390/md13085102.
959. C. J. Smith, R. L. Hettich, J. Jompa, A. Tahir, M. V. Buchanan and C. M. Ireland, J. Org. Chem., 1998, 63, 4147–4150,  DOI:10.1021/jo980171a.
960. W. Wang, H. Kim, S. J. Nam, B. J. Rho and H. Kang, J. Nat. Prod., 2012, 75, 2049–2054,  DOI:10.1021/np300544a.
961. A. Boulangé, J. Parraga, A. Galán, N. Cabedo, S. Leleu, M. Jesus Sanz, D. Cortes and X. Franck, Bioorg. Med. Chem., 2015, 23, 3618–3628,  DOI:10.1016/j.bmc.2015.04.010.
962. J. Boukouvalas and C. Thibault, J. Org. Chem., 2015, 80, 681–684,  DOI:10.1021/jo502503w.
963. S. Miao and R. J. Andersen, J. Org. Chem., 1991, 56, 6275–6280,  DOI:10.1021/jo00022a012.
964. U. A. Pereira, L. C. A. Barbosa, A. J. Demuner, A. A. Silva, M. Bertazzini and G. Forlani, Chem. Biodiversity, 2015, 12, 987–1006,  DOI:10.1002/cbdv.201400416.
965. L. H. Franco, J. Nat. Prod., 1998, 61, 1130–1132,  DOI:10.1021/np970493u.
966. R. R. Yadav, S. I. Khan, S. Singh, I. A. Khan, R. A. Vishwakarma and S. B. Bharate, Eur. J. Med. Chem., 2015, 98, 160–169,  DOI:10.1016/j.ejmech.2015.05.020.
967. R. G. S. Berlinck, R. Britton, E. Piers, L. Lim and M. Roberge, J. Org. Chem., 1998, 63, 9850–9856,  DOI:10.1021/jo981607p.
968. H. Lavrard, B. Salvetti, V. Mathieu, F. Rodriguez, R. Kiss and E. Delfourne, ChemMedChem, 2015, 10, 607–609,  DOI:10.1002/cmdc.201500025.
969. R. J. Andersen, D. J. Faulkner and H. Cun-heng, J. Am. Chem. Soc., 1985, 107, 5492–5495,  DOI:10.1021/ja00305a027.
970. A. Theppawong, P. Ploypradith, P. Chuawong, S. Ruchirawat and M. Chittchang, Chem.–Asian J., 2015, 10, 2631–2650,  DOI:10.1002/asia.201500611.
971. T. Maoka, S. Nakachi, R. Kobayashi, M. Mori and Y. Sakagami, Tetrahedron Lett., 2015, 56, 5954–5955,  DOI:10.1016/j.tetlet.2015.09.060.
972. T. Maoka, N. Akimoto, Y. Terada, S. Komemushi, R. Harada, N. Sameshima and Y. Sakagami, J. Nat. Prod., 2010, 73, 675–678,  DOI:10.1021/np100021u.
973. Y. Yamano, K. Ematsu, H. Kurimoto, T. Maoka and A. Wada, Mar. Drugs, 2015, 13, 159–172,  DOI:10.3390/md13010159.
974. X.-W. Yang, Z. Miao, X.-N. Ma, G.-Y. Zhang, A. Steinmetz, B. Yang, J.-F. Wang, J. Liu, Y. Liu and N. Wang, Tetrahedron Lett., 2015, 56, 6174–6176,  DOI:10.1016/j.tetlet.2015.09.019.
975. T. Malyarenko, O. Malyarenko (Vishchuk), N. Ivanchina, A. Kalinovsky, R. Popov and A. Kicha, Mar. Drugs, 2015, 13, 4418–4435,  DOI:10.3390/md13074418.
976. S. Yu, X. Ye, H. Huang, R. Peng, Z. Su, X.-Y. Lian and Z. Zhang, Planta Med., 2015, 81, 152–159,  DOI:10.1055/s-0034-1383404.
977. A. A. Kicha, A. I. Kalinovsky, T. V. Malyarenko, N. V. Ivanchina, P. S. Dmitrenok, E. S. Menchinskaya, E. A. Yurchenko, E. A. Pislyagin, D. L. Aminin, T. T. T. Huong, P. Quoc Long and V. A. Stonik, J. Nat. Prod., 2015, 78, 1397–1405,  DOI:10.1021/acs.jnatprod.5b00332.
978. N. Xuan Cuong, L. Thi Vien, T. T. Hong Hanh, N. P. Thao, D. T. Thao, N. V. Thanh, N. H. Nam, D. C. Thung, P. V. Kiem and C. V. Minh, Bioorg. Med. Chem. Lett., 2015, 25, 3151–3156,  DOI:10.1016/j.bmcl.2015.06.005.
979. B. T. Ngoan, T. T. Hong Hanh, L. T. Vien, C. N. Diep, N. P. Thao, D. T. Thao, N. V. Thanh, N. X. Cuong, N. H. Nam, D. C. Thung, P. V. Kiem, Y. H. Kim and C. V. Minh, J. Asian Nat. Prod. Res., 2015, 17, 1010–1017,  DOI:10.1080/10286020.2015.1041930.
980. A. S. Silchenko, A. I. Kalinovsky, P. S. Dmitrenok, V. I. Kalinin, A. N. Mazeika, N. S. Vorobieva, N. M. Sanina and E. Y. Kostetsky, Nat. Prod. Commun., 2015, 10, 877–957.
981. A. S. Silchenko, A. I. Kalinovsky, S. A. Avilov, P. V. Andryjaschenko, P. S. Dmitrenok, E. A. Yurchenko, I. Yu. Dolmatov and V. I. Kalinin, Carbohydr. Res., 2015, 414, 22–31,  DOI:10.1016/j.carres.2015.06.005.
982. Y. Bahrami and C. Franco, Mar. Drugs, 2015, 13, 597–617,  DOI:10.3390/md13010597.
983. A. S. Silchenko, A. I. Kalinovsky, S. A. Avilov, P. V. Andryjaschenko, P. S. Dmitrenok, E. A. Yurchenko, I. Y. Dolmatov, V. I. Kalinin and V. A. Stonik, Nat. Prod. Commun., 2013, 8, 1527–1534.
984. A. I. Kalinovsky, A. S. Silchenko, S. A. Avilov and V. I. Kalinin, Nat. Prod. Commun., 2015, 10, 1167–1237.
985. H. Tamai, A. Imamura, J. Ogawa, H. Ando, H. Ishida and M. Kiso, Eur. J. Org. Chem., 2015, 2015, 5199–5211,  DOI:10.1002/ejoc.201500606.
986. R. Higuchi, K. Inukai, J. X. Jhou, M. Honda, T. Komori, S. Tsuji and Y. Nagai, Liebigs Ann. Chem., 1993, 359–366,  DOI:10.1002/jlac.199319930161.
987. K. Goto, T. Suzuki, H. Tamai, J. Ogawa, A. Imamura, H. Ando, H. Ishida and M. Kiso, Asian J. Org. Chem., 2015, 4, 1160–1171,  DOI:10.1002/ajoc.201500282.
988. K. Pan, C. Tanaka, M. Inagaki, R. Higuchi and T. Miyamoto, Mar. Drugs, 2012, 10, 2467–2480,  DOI:10.3390/md10112467.
989. Y. Dai and B. Yu, Chem. Commun., 2015, 51, 13826–13829,  10.1039/c5cc04734J.
990. N. P. Thao, N. X. Cuong, B. T. Thuy Luyen, N. V. Thanh, N. X. Nhiem, Y.-S. Koh, B. M. Ly, N. H. Nam, P. V. Kiem, C. v. Minh and Y. H. Kim, J. Nat. Prod., 2013, 76, 1764–1770,  DOI:10.1021/np400492a.
991. D. Zhu and B. Yu, J. Am. Chem. Soc., 2015, 137, 15098–15101,  DOI:10.1021/jacs.5b11276.
992. J. Qi, M. Ojika and Y. Sakagami, Bioorg. Med. Chem., 2002, 10, 1961–1966,  DOI:10.1016/s0968-0896(02)00006-8.
993. R. E. Moore, H. Singh and P. J. Scheuer, J. Org. Chem., 1966, 31, 3645–3650,  DOI:10.1021/jo01349a040.
994. E. Pena-Cabrera and L. S. Liebeskind, J. Org. Chem., 2002, 67, 1689–1691,  DOI:10.1021/jo016034m.
995. H. K. Kim, J. B. Youm, S. H. Jeong, S. R. Lee, I.-S. Song, T. H. Ko, J. R. Pronto, K. S. Ko, B. D. Rhee, N. Kim, B. Nilius, N. P. Mischchenko, S. A. Fedoreyev, V. A. Stonik and J. Han, Pfluegers Arch., 2015, 467, 2151–2163,  DOI:10.1007/s00424-014-1648-2.
996. D. Y. Seo, R. A. McGregor, Su J. Noh, S. J. Choi, N. P. Mishchenko, S. A. Fedoreyev, V. A. Stonik and J. Han, Mar. Drugs, 2015, 13, 5722–5731,  DOI:10.3390/md13095722.
997. M. Inagaki, R. Isobe and R. Higuchi, Eur. J. Org. Chem., 1999, 771–774,  DOI:10.1002/(sici)1099-0690(199904)1999.
998. M. Yamagishi, R. Hosoda-Yabe, H. Tamai, M. Konishi, A. Imamura, H. Ishida, T. Yabe, H. Ando and M. Kiso, Mar. Drugs, 2015, 13, 7250–7274,  DOI:10.3390/md13127062.
999. N. P. Thao, B. T. Thuy Luyen, E. J. Kim, J. I. Kang, H. K. Kang, N. X. Cuong, N. H. Nam, P. V. Kiem, C. V. Minh and Y. H. Kim, J. Med. Food, 2015, 18, 45–53,  DOI:10.1089/jmf.2013.3105.
1000. N. Thao, B. Luyen, J. Koo, S. Kim, Y. Koh, N. Cuong, N. Nam, P. Van Kiem, Y. Kim and C. Van Minh, Biol. Res., 2015, 48, 12,  DOI:10.1186/s40659-015-0002-2.
1001. S. Yu, X. Ye, L. Chen, X. Xie, Q. Zhou, X.-Y. Lian and Z. Zhang, Phytomedicine, 2015, 22, 1112–1119,  DOI:10.1016/j.phymed.2015.08.007.
1002. S.-H. Yun, E.-S. Park, S.-W. Shin, M.-H. Ju, J.-Y. Han, J.-S. Jeong, S.-H. Kim, V. A. Stonik, J.-Y. Kwak and J.-I. Park, Oncotarget, 2015, 6, 27596–27612,  DOI:10.18632/oncotarget.4820.
1003. X.-X. Yi, J.-G. Deng, C.-H. Gao, X.-T. Hou, F. Li, Z.-P. Wang, E.-W. Hao, Y. Xie, Z.-C. Du, H.-X. Huang and R.-M. Huang, Molecules, 2015, 20, 14565–14575,  DOI:10.3390/molecules200814565.
1004. D.-M. Yan, C.-H. Gao, X.-X. Yi, W.-P. Xie, M.-B. Xu and R.-M. Huang, Z. Naturforsch., B: J. Chem. Sci., 2015, 70, 691–694,  DOI:10.1515/znb-2014-0111.
1005. T.-H.-T. Nguyen, H.-V.-T. Pham, N.-K.-T. Pham, N.-D.-P. Quach, K. Pudhom, P. Erik Hansen and K.-P.-P. Nguyen, Bioorg. Med. Chem. Lett., 2015, 25, 2366–2371,  DOI:10.1016/j.bmcl.2015.04.017.
1006. L. Duc Dat, N. P. Thao, B. H. Tai, B. T. Thuy Luyen, S. Kim, J. E. Koo, Y. Sang Koh, N. T. Cuong, N. V. Thanh, N. X. Cuong, N. H. Nam, P. V. Kiem, C. V. Minh and Y. H. Kim, Bioorg. Med. Chem. Lett., 2015, 25, 1412–1416,  DOI:10.1016/j.bmcl.2015.02.048.
1007. A. Panyadee, P. Sahakitpichan, S. Ruchirawat and T. Kanchanapoom, Phytochem. Lett., 2015, 11, 215–219,  DOI:10.1016/j.phytol.2014.12.021.
1008. S. C. H. V. Appa Rao Annam, M. Ankireddy, M. Babu Sura, M. G. Ponnapalli, A. V. S. Sarma and B. S. Jeelani, Org. Lett., 2015, 17, 2840–2843,  DOI:10.1021/acs.orglett.5b01257.
1009. Y. Yang, Y. Zhang, D. Liu, M. Li-Weber, B. Shao and W. Lin, Fitoterapia, 2015, 103, 277–282,  DOI:10.1016/j.fitote.2015.04.016.
1010. W. Li, Z. Jiang, L. Shen, P. Pedpradab, T. Bruhn, J. Wu and G. Bringmann, J. Nat. Prod., 2015, 78, 1570–1578,  DOI:10.1021/acs.jnatprod.5b00151.
1011. Y.-B. Wu, D. Liu, P.-Y. Liu, X.-M. Yang, M. Liao, N.-N. Lu, F. Sauriol, Y.-C. Gu, Q.-W. Shi, H. Kiyota and M. Dong, Helv. Chim. Acta, 2015, 98, 691–698,  DOI:10.1002/hlca.201400290.
1012. S. Khan, N. Riaz, N. Afza, A. Malik, Aziz-ur-Rehman, L. Iqbal and M. Lateef, J. Asian Nat. Prod. Res., 2009, 11, 44–48,  DOI:10.1080/10286020802435745.
1013. A. S. Anjaneyulu and V. L. Rao, Nat. Prod. Lett., 2001, 15, 13–19,  DOI:10.1080/10575630108041252.
1014. K. Pudhom, D. Sommit, P. Nuclear, N. Ngamrojanavanich and A. Petsom, J. Nat. Prod., 2010, 73, 263–266,  DOI:10.1021/np900583h.
1015. Y. Zhang, Z. Deng, T. Gao, P. Proksch and W. Lin, Phytochemicals, 2005, 66, 1465–1471,  DOI:10.1016/j.phytochem.2005.04.018.
1016. J. Neumann, Y. Yang, R. Köhler, M. Giaisi, M. Witzens-Harig, D. Liu, P. H. Krammer, W. Lin and M. Li-Weber, Int. J. Cancer, 2015, 137, 2739–2748,  DOI:10.1002/ijc.29629.
1017. X. Luo, Y. Huang, S. Zhang, H. Yin, C. Li and Q. Li, Biochem. Syst. Ecol., 2014, 56, 191–195,  DOI:10.1016/j.bse.2014.05.018.
1018. H. Tang, H. Ge, Z.-B. Chen, X.-M. Luo, F.-J. Su, Y.-B. Liang, Z.-Y. Li, J.-G. Wu, Q. Yang, L.-J. Zeng and Z.-F. Ma, Mar. Drugs, 2015, 13, 5593–5605,  DOI:10.3390/md13095593.
1019. J. D. Connolly, M. MacLellan, D. A. Okorie and D. A. H. Taylor, J. Chem. Soc., Perkin Trans. 1, 1976, 1993–1996,  10.1039/P19760001993.
1020. K. A. Alvi, P. Crews, B. Aalbersberg and R. Prasad, Tetrahedron, 1991, 47, 8943–8948,  DOI:10.1016/s0040-4020(01)86500-5.
1021. V. Lakshmi, V. Mishra and G. Palit, Nat. Prod. Res., 2015, 29, 469–473,  DOI:10.1080/14786419.2014.950959.
1022. K. Mary Elizabeth Gnanambal, J. Patterson and E. J. K. Patterson, Phytother. Res., 2015, 29, 554–560,  DOI:10.1002/ptr.5283.
1023. G. R. Pettit, J.-P. Xu, J.-C. Chapuis and N. Melody, J. Nat. Prod., 2015, 78, 1446–1450,  DOI:10.1021/acs.jnatprod.5b00129.
1024. G. R. Pettit, B. R. Moser, D. L. Herald, J. C. Knight, J.-C. Chapuis and X. Zheng, J. Nat. Prod., 2015, 78, 1067–1072,  DOI:10.1021/np501033u.
1025. T. V. Ovchinnikova, G. M. Aleshina, S. V. Balandin, A. D. Krasnosdembskaya, M. L. Markelov, E. I. Frolova, Y. F. Leonova, A. A. Tagaev, E. G. Krasnodembsky and V. N. Kokryakov, FEBS Lett., 2004, 577, 209–214,  DOI:10.1016/j.febslet.2004.10.012.
1026. P. V. Panteleev, I. A. Bolosov, S. V. Balandin and T. V. Ovchinnikova, J. Pept. Sci., 2015, 21, 105–113,  DOI:10.1002/psc.2732.
1027. L. Wei, J. Gao, S. Zhang, S. Wu, Z. Xie, G. Ling, Y.-Q. Kuang, Y. Yang, H. Yu and Y. Wang, J. Biol. Chem., 2015, 290, 16633–16652,  DOI:10.1074/jbc.M115.642645.
1028. B.-W. Ding, P. Naumov and Y.-J. Liu, J. Chem. Theory Comput., 2015, 11, 591–599,  DOI:10.1021/ct5009203.
1029. Y. Han, Z. Cui, Y.-H. Li, W.-H. Hsu and B.-H. Lee, Mar. Drugs, 2015, 14, 2,  DOI:10.3390/md14010002.
1030. A. R. Osborn, K. H. Almabruk, G. Holzwarth, S. Asamizu, J. LaDu, K. M. Kean, P. Andrew Karplus, R. L. Tanguay, A. T. Bakalinsky and T. Mahmud, eLife, 2015, 4, e05919,  DOI:10.7554/elife.05919.
1031. G. R. Pettit, J. F. Day, J. L. Hartwell and H. B. Wood, Nature, 1970, 227, 962,  DOI:10.1038/227962a0.
1032. G. R. Pettit, P. M. Arce, J.-C. Chapuis and C. B. Macdonald, J. Nat. Prod., 2015, 78, 510–523,  DOI:10.1021/np501004h.
1033. M. M. Sigel, L. L. Welham, W. Lichter, L. E. Duden, H. Gargus and A. H. Lucas, in Food-Drugs from the Sea: Proceedings, ed. H. W. Youngken Jr, Mar. Tech. Soc., 1969, pp. 281–294.
1034. A. E. Wright, D. A. Forleo, G. P. Gunawardana, S. P. Gunasekera, F. E. Koehn and O. J. McConnell, J. Org. Chem., 1990, 55, 4508–4512,  DOI:10.1021/jo00302a006.
1035. K. L. Rinehart, T. G. Holt, N. L. Fregeau, J. G. Stroh, P. A. Keifer, F. Sun, L. H. Li and D. G. Martin, J. Org. Chem., 1990, 55, 4512–4515,  DOI:10.1021/jo00302a007.
1036. C. Cuevas and A. Francesch, Nat. Prod. Rep., 2009, 26, 322–337,  10.1039/b808331m.
1037. Firmicutes 57, Annelida 24, Ciliophora 19, Bacteroidetes 16, Hemichordata 12, Bacillariophyta 11, Arthropoda 10, Haptophyta 10, Basidiomycota 3, Euryarchaeota 3, Miozoa 3, Cryptophyta 2, Nematoda 2, Platyhelminthes 2, Euglenozoa 1, Labyrinthulomycota 1.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6np00124f

---