Editorial: Synthesis themed issue

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Abstract

With this issue, NPR fully embraces the molecular and structural biology revolution by showcasing leading work in natural product synthesis, with emphasis on those areas allied to the chemical biology agenda.

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Professor David O'Hagan is Head of Organic Chemistry at St Andrews University in Scotland and was until recently the Chair of the Editorial Board of NPR.

 

Natural Product Reports is 25 years old as a journal, and over that time the editorial board has energetically pursued authors to ensure coverage of contemporary developments in all aspects of natural products, focusing on new structures, bioactivities, and innovations and developments of biosynthetic pathways across all structural classes. This has embraced the characterisation and roles of individual biosynthetic enzymes and the underlying genetic basis of secondary metabolite production in organisms as diverse as bacteria, fungi, plants and marine micro- and macro-organisms.

Historically, although synthesis has been covered quite regularly in reviews, it has not been a central theme for NPR, due largely to the size of the field and being a territory which is covered by many specialist organic chemistry journals. However, progress in the chemical biology agenda is being enriched by access to molecules of increasing structural sophistication for the intervention and evaluation of biological processes and phenomena. Not only that, but the art of total synthesis has developed to the point where, in skilled hands, molecules of increasing complexity are being assembled in an impressive and apparently straightforward manner. The editorial board of NPR seek now to solicit world-class reviews in natural product synthesis, particularly where the synthesis enables a deeper understanding of biology, provides tools for exploring biology or contributes mechanistic insights into developing biosynthetic hypotheses. This themed issue formally launches this synthesis agenda for NPR.

In this issue we have been able to assemble an outstanding group of reviews:

Mark S. Tichenor and Dale Boger describe in their Highlight the synthesis and evaluation of the DNA alkylator yatakemycin. Their synthesis studies have led to a structural re-evaluation of the natural product and provide important mechanistic insights into the mode of action of this intriguing metabolite (DOI: 10.1039/b705665f).

Mathilde Lachia and Chris Moody review synthesis and structural studies on the marine antitumour metabolite diazonamide A, and demonstrate the increasing role of total synthesis as the ultimate authority in structural elucidation (DOI: 10.1039/b705663j).

In a combined contribution from academia and industry, Paul Bulger, Sharan Bagal and Rodolfo Marquez give the definitive account on the status of synthetic biomimetic studies, which stimulate and suggest intriguing biosynthetic hypotheses for the assembly of complex structural skeletons (DOI: 10.1039/b705909b).

Paul Roethle and Dirk Trauner extend such insights by describing their (and others’) biomimetic-inspired total synthesis approaches to a series of highly functionalised carbocyclic marine metabolite skeletons (DOI: 10.1039/b705660p).

Torsten Busch and Andreas Kirschning describe synthetic approaches to various classes of complex plant terpenes including the ginkgolides, tonantzitlolone, ingenol and eleutherobin. These compounds present unique synthetic challenges due to their structural complexity, challenges which need to be overcome to access their pharmaceutical potential (DOI: 10.1039/b705652b).

Gordon Florence, Nicola Gardner and Ian Paterson illustrate that the science of total synthesis has been sufficiently mastered to entertain the de novo synthesis of complex marine natural products on a multi-gram scale for clinical trials. This is illustrated in a review of two flagship projects: the scaling-up of the synthesis of the marine metabolites discodermolide and dictyostatin. These are compounds of high potency with potential in oncology, but unavailable by fermentation because the organisms producing them have evaded isolation and characterisation (DOI: 10.1039/b705661n).

Jonathan Sperry, Prabhakar Bachu and Margaret Brimble from New Zealand report on the isolation, bioactivity and synthesis strategies to the pyranonaphthoquinone antibiotics, a class of compounds of bacterial and fungal origin with potential in cancer chemotherapy (DOI: 10.1039/b708811f).

Makoto Sasaki and Haruhiko Fuwa contribute from Japan an account of their total synthesis studies on marine polycyclic ethers, and convey the challenges and excitement in accessing these structural skeletons, which are among the most elaborate secondary metabolites that are found in nature (DOI: 10.1039/b705664h).

It has been a great pleasure to be involved in gathering together these papers for this themed issue, and we thank the authors for their contributions and patience in bringing their copy to publication.

We now encourage the synthesis community to engage with NPR as an appropriate forum in which to review important developments in natural product total synthesis allied to the chemical biology agenda.

David O'Hagan, Guest Editor

Vikki Allen, Editor, NPR

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