Lendenfeldaranes W–Y, new 24-homoscalaranes from a marine sponge Lendenfeldia species

Abstract

Three new scalarane-type sesterterpenoids, lendenfeldaranes W–Y (1–3), along with a known analogue, lendenfeldarane D (4), were isolated from a marine sponge identified as Lendenfeldia species. The structures of all isolates were determined based on spectroscopic methods. Scalarane 1 exhibited significant activity in enhancing alkaline phosphatase (ALP) activity.

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1 Introduction

Sponges of the genus Lendenfeldia (phylum Porifera, class Demospongiae, subclass Keratosa, order Dictyoceratida, family Thorectidae, subfamily Phyllospongiinae) are broadly distributed across shallow coral reefs in the Asia–Pacific region. These marine invertebrates have attracted significant scientific attention owing to their rich repertoire of secondary metabolites, many of which display noteworthy pharmacological potential. Among these, sesterterpenoids-particularly 26-carbon homoscalarane and 24-homoscalarane derivatives, represent the dominant chemical constituents of Lendenfeldia species. A variety of biological activities have been reported for these compounds, including anti-inflammatory,^1–4 cytotoxic,^5–11 antimicrobial,^12–14 and anti-osteoporotic effects,¹⁵ understanding their promise as valuable leads in drug discovery and biomedical research.

In our previous work, we reported the isolation of a series of scalarane-type sesterterpenoids from a Lendenfeldia sponge collected in the coastal waters of Taiwan, together with an evaluation of their biological activities. Building on this research, we have now isolated three new 24-homoscalaranes, designated lendenfeldaranes W–Y (1–3), along with a known analogue, lendenfeldarane D (4) (ref. 9) (Fig. 1). The structures of compounds 1–3 were established through detailed spectroscopic analyses. Furthermore, their anti-osteoporotic potential was assessed by examining their ability to enhance ALP activity in MG63 osteoblast-like cells.

Fig. 1 Structures of lendenfeldaranes W–Y (1–3), lendenfeldarane D (4), felixin B (5), and felixin A (6).

2 Results and discussion

Lendenfeldarane W (1) was obtained as an amorphous solid. The molecular formula was determined to be C₂₈H₄₄O₆ from the (+)-HRESIMS ion at m/z 499.30284 [M + Na]⁺ (calcd for C₂₈H₄₄O₆ + Na, 499.30301), corresponding to seven degrees of unsaturation. The IR spectrum showed absorptions at 3419 and 1735 cm⁻¹, indicating the presence of hydroxy and ester carbonyl groups.

The ¹H NMR data for 1 (Table 1) displayed four tertiary methyl singlets at δ_H 0.78 (H₃-20), 0.84 (H₃-23), 0.89 (H₃-19), and 1.08 (H₃-21); one secondary methyl doublet at δ_H 1.18 (3H, d, J = 6.6 Hz, H₃-26); two olefinic protons at δ_H 5.98 (1H, dd, J = 10.2, 2.4 Hz, H-15) and 5.71 (1H, dd, J = 10.2, 3.0 Hz, H-16); and three oxymethine protons at δ_H 5.28 (1H, d, J = 3.0 Hz, H-25), 4.96 (1H, dd, J = 3.0, 3.0 Hz, H-12), and 4.41 (1H, q, J = 6.6 Hz, H-24). In addition, an oxymethylene group was evident from the diastereotopic geminal protons at δ_H 4.04 (1H, d, J = 12.0 Hz, H-20a) and 3.88 (1H, d, J = 12.0 Hz, H-20b). The ¹³C NMR and HSQC spectra revealed 28 carbon signals (Table 1), comprising one 1,2-disubstituted double bond (δ_C 132.2/CH-15; 127.4/CH-16), one acetal carbon (δ_C 97.8/CH-25), one oxygenated quaternary carbon (δ_C 80.2/C-17), two oxymethines (δ_C 85.1/CH-24; 74.1/CH-12), one oxymethylene (δ_C 62.6/CH₂-22), four tertiary methyls (δ_C 33.9/CH₃-19; 21.9/CH₃-20; 17.3/CH₃-21; 16.6/CH₃-23), one secondary methyl (δ_C 15.7/CH₃-26), six aliphatic methylenes (δ_C 41.7/CH₂-3; 41.5/CH₂-7; 34.0/CH₂-1; 25.1/CH₂-11; 18.3/CH₂-2; 17.6/CH₂-6), four aliphatic methines (δ_C 62.8/CH-18; 57.0/CH-5; 52.5/CH-9; 52.0/CH-14), four non-oxygenated quaternary carbons (δ_C 41.7/C-10; 36.7/C-8; 33.0/C-4; 42.1/C-13), and one acetoxy group (δ_C 21.4/acetate methyl; 170.4/acetate carbonyl).

Table 1 ¹H and ¹³C NMR data for lendenfeldaranes W–Y (1–3)

Position	1		2		3
	δH^a (J in Hz)	δC^b, Mult.^c	δH^a (J in Hz)	δC^b, Mult.^c	δH^a (J in Hz)	δC^b, Mult.^c
a Spectra recorded at 600 MHz in CDCl3.b Spectra recorded at 150 MHz in CDCl3.c Multiplicity was deduced by ^13C, HSQC, and HMBC spectra.d Signals overlapped.e — signals were not observed.
1α	0.59 dddd (13.2, 13.2, 3.6, 1.2)	34.0, CH2	0.55 dddd (13.8, 13.8, 3.6, 1.2)	34.6, CH2	0.53 dddd (13.2, 13.2, 3.6, 1.2)	34.5, CH2
β	2.10 br d (13.2)		1.99 m		2.13 m
2α	1.47 ddddd (18.0, 3.6, 3.6, 3.6, 3.6)	18.3, CH2	1.44 m^d	18.2, CH2	1.45 m^d	18.4, CH2
β	1.56 m^d		1.56 m		1.54 m
3α	1.44 m	41.7, CH2	1.46 m	41.4, CH2	1.44 br d (13.2)^d	41.6, CH2
β	1.21 dd (13.2, 3.6)		1.14 m		1.19 dd (13.2, 4.8)
4		33.0, C		33.0, C		32.9, C
5	1.01 dd (13.2, 2.4)	57.0, CH	1.02 dd (12.0, 1.8)	57.1, CH	1.00 dd (12.0, 1.8)	56.6, CH
6α	1.56 m^d	17.6, CH2	1.60 m	17.7, CH2	4.60 m	68.4, CH
β	1.41 ddd (13.2, 13.2, 3.6)		1.44 m^d
7α	1.06 ddd (13.2, 12.6, 3.6)	41.5, CH2	1.11 ddd (13.2, 13.2, 4.2)	40.8, CH2	1.40 m^d 2.18 m	44.3, CH2
β	1.97 ddd (12.6, 3.6, 3.6)		1.80 ddd (13.2, 3.6, 3.6)
8		36.7, C		37.2, C		39.1, C
9	1.35 br d (12.6)	52.5, CH	1.40 dd (13.2, 4.2)	52.7, CH	1.40 br d (13.8)^d	53.0, CH
10		41.7, C		40.1, C		—^e
11α	1.88 ddd (15.0, 3.0, 2.4)	25.1, CH2	2.07 m	24.3, CH2	1.98 m	25.0, CH2
β	2.26 ddd (15.0, 12.6, 3.0)				2.17 m
12	4.96 dd (3.0, 3.0)	74.1, CH	5.00 dd (3.0, 2.4)	76.0, CH	4.63 dd (3.0, 1.8)	77.6, CH
13		42.1, C		41.2, C		39.5, C
14	2.14 dd (3.0, 2.4)	52.0, CH	2.12 dd (14.4, 4.2)	48.8, CH	1.57 m	56.1, CH
15	5.98 dd (10.2, 2.4)	132.2, CH	2.55 dd (17.4, 4.2)-Hα	34.9, CH2	2.26 m 2.34 m^d	—^e
			2.43 dd (17.4, 14.4)-Hβ
16	5.71 dd (10.2, 3.0)	127.4, CH		197.4, C	6.64 dd (3.0, 3.0)	139.6, CH
17		80.2, C		136.7, C		—^e
18	2.47 s	62.8, CH	7.31 s	163.5, CH	1.93 d (17.4)-Hα	35.2, CH2
					2.27 br d (17.4)-Hβ
19	0.89 s	33.9, CH3	0.89 s	33.7, CH3	0.88 s	33.8, CH3
20	0.78 s	21.9, CH3	0.84 s	21.8, CH3	0.78 s	21.9, CH3
21	1.08 s	17.3, CH3	1.01 s	15.8, CH3	1.24 s	16.9, CH3
22a	4.04 d (12.0)	62.6, CH2	4.63 d (12.0)	64.6, CH2	4.05 d (11.4)	62.9, CH2
b	3.88 d (12.0)		4.12 d (12.0)		3.92 dd (11.4, 1.2)
23	0.84 s	16.6, CH3	1.17 s	18.6, CH3	0.92 s	20.8, CH3
24	4.41 q (6.6)	85.1, CH		197.8, C		199.4, C
25	5.28 d (3.0)	97.8, CH	2.44 s	30.7, CH3	2.34 s^d	25.4, CH3
26	1.18 d (6.6)	15.7, CH3
OAc-12	2.15 s	170.4, C	2.07 s	170.3, C 21.2, CH3	2.10 s	170.1, C
		21.4, CH3				21.4, CH3
OAc-22			2.07 s	170.8, C
				21.2, CH3
OH-17	2.31 br s
OH-25	2.73 br d (3.0)

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Analysis of the NMR data indicated that two degrees of unsaturation were attributed to one acetoxy group and a 1,2-disubstituted olefin, while the remaining five degrees of unsaturation defined a pentacyclic homoscalarane skeleton. This inference was supported by the ¹H–¹H COSY correlations of 1 (Fig. 2), which established six partial spin systems: H₂-1/H₂-2/H₂-3, H-5/H₂-6/H₂-7, H-9/H₂-11/H-12, H-14/H-15/H-16, H-18/H-25, and H-24/H₃-26. Key ²J- and ³J-HMBC correlations from protons to quaternary carbons, such as H₂-3, H-5/C-4; H₂-7, H-9, H-15/C-8; H-5, H-9/C-10; H-15, H-18, H-25/C-13; and H-15, H-16, H-18, H-24, H-25, H₃-26/C-17, confirmed a 6/6/6/6/5 fused pentacyclic 24-homoscalarane framework.

Fig. 2 Key COSY and HMBC correlations of 1.

The oxymethylene unit (δ_C 62.6) correlated with the methylene protons at δ_H 4.04 and 3.88 in the HSQC spectrum, and these protons showed ²J- and ³J-HMBC correlations to C-10 (δ_C 41.7), C-1 (δ_C 34.0) and C-9 (δ_C 52.5), indicating a hydroxymethyl substituent at C-10 (Fig. 2). Further HMBC correlations, H₃-19/C-3, C-4, C-5, C-20; H₃-20/C-3, C-4, C-5, C-19; H₃-21/C-7, C-8, C-9, C-14; H₃-23/C-12, C-13, C-14, C-18; and H₃-26/C-17, C-24, established the position of Me-19, Me-20, Me-21, Me-23, and Me-26 at C-4, C-4, C-8, C-13, and C-24, respectively.

An acetoxy substituent was placed at C-12, an oxymethine center, based on the chemical shifts of H-12 (δ_H 4.96, dd, J = 3.0, 3.0 Hz) and C-12 (δ_C 74.1), which closely matched those reported for felixin D (δ_H 4.91, dd, J = 3.2, 2.4 Hz; δ_C 74.6),⁶ a known 24-homoscalarane analogue possessing an identical functional group. Although no HMBC correlation was observed between H-12 and the acetate carbonyl, the substitution pattern was confirmed by comparison. The hydroxy group at C-25 was deduced from the COSY correlation between the hydroxy proton (δ_H 2.73, d, J = 3.0 Hz, OH-25) and the acetal proton at δ_H 5.28 (br d, J = 3.0 Hz, H-25). Formation of a cyclic ether linkage between C-24 and C-25 was evidenced by the HMBC correlation from H-25 (δ_H 5.28) to the oxymethine carbon at C-24 (δ_C 85.1). The chemical shift of C-25 (δ_C 97.8) was consistent with its assignment as an acetal carbon.

Of the six oxygen atoms in the molecular formula, five were accounted for by an acetal (including one hydroxy group), an additional hydroxy group, and an acetoxy substituent. The remaining oxygen atom was assigned as a hydroxy group attached to C-17, supported by the downfield chemical shift of the oxygenated quaternary carbon (δ_C 80.2).

The stereochemistry of 1 was determined by analysis of NOE correlations in the NOESY spectrum (Fig. 3). Following the established convention for scalarane-type sesterterpenoids, H-5 and the hydroxymethyl group at C-10 were assigned to the α- and β-faces, respectively, based on the absence of an NOE correlation between H-5 and H₂-22.^16,17 In the NOESY spectrum of 1, H-9 showed correlations with H-5 and H-14, but not with H₃-21 and H₂-22, indicating that H-9 and H-14 reside on the α face, whereas Me-21 and the C-10 hydroxymethyl group are positioned on the β-face. Correlations of H₃-23 with both H₃-21 and H-12 established the β-orientations of Me-23 and H-12. H-18 correlated with H-14, but not with H₃-23, placing H-18 on the α-face, while H-25 correlated with H-12 and H₃-23, supporting its β-orientation. Additionally, a correlation between H-15 and H-16 confirmed the Z-geometry of the C-15/16 double bond. The hydroxy proton at C-25 (OH-25) showed correlation with OH-17, indicating the α-orientation of the hydroxy group at C-17. Taken together, these data established the absolute configuration of 1 as 5S, 8R, 9S, 10R, 12S, 13S, 14S, 17R, 18R, 24S, 25R. Notably, compound 1 represents the first reported example of a 17-hydroxy scalarane derivative.

Fig. 3 Stereo-view of 1 (generated by computer modeling) and calculated distances (Å) between selected protons with key NOESY correlations.

Lendenfeldarane X (2) was assigned a molecular formula of C₂₉H₄₂O₆ based on its (+)-HRESIMS ion at m/z 509.28714 (calcd for C₂₉H₄₂O₆ + Na, 509.28736), corresponding to nine degrees of unsaturation. Analysis of the ¹H and ¹³C NMR data (Table 1) indicated that 2 belongs to the 24-homoscalarane class, closely resembling the known analogue felixin B (5) (Fig. 1), originally isolated from the Formosan marine sponge Ircinia felix.⁶ The key structural difference between 2 and 5 lies in the substitution at C-10: in 5, a hydroxymethyl group is present (δ_H 4.03, 1H, d, J = 11.6 Hz; 3.89, 1H, d, J = 11.6 Hz/δ_C 63.0, CH₂-22; δ_C 41.8, C-10),⁶ whereas in 2 this functionality is replaced by an acetoxymethyl group (δ_H 4.63, 1H, d, J = 12.0 Hz; 4.12, 1H, d, J = 12.0 Hz/δ_C 64.6, CH₂-22; δ_C 40.1, C-10). Detailed interpretation of the 2D NMR spectroscopic data of 2 corroborated this substitution, thereby establishing its planar structure (Fig. 4).

Fig. 4 Key COSY and HMBC correlations of 2.

NOESY correlations of 2 established the configurations of the stereogenic centers in rings A–D, which were consistent with those of 1 and 5 (Fig. 5). The olefinic proton H-18 (δ_H 7.31) exhibited correlations with H-12 (δ_H 5.00) and H₃-23 (δ_H 1.17), but not with the acetyl methyl H₃-25 (δ_H 2.44), supporting an s-cis diene configuration for C-18/17/24. Based on these data, the stereogenic carbons were assigned as 5S, 8R, 9S, 10R, 12S, 13S, 14S. Thus, the structure of lendenfeldarane X (2) was established.

Fig. 5 Stereo-view of 2 (generated by computer modeling) and calculated distances (Å) between selected protons with key NOESY correlations.

Lendenfeldarane Y (3) was obtained as an amorphous powder with the molecular formula C₂₇H₄₂O₅, established by (+)-HRESIMS at m/z 469.29239 (calcd for C₂₇H₄₂O₅ + Na, 469.29245), indicating seven degrees of unsaturation. IR absorptions at 3443, 1731, and 1664 cm⁻¹ revealed hydroxy, ester carbonyl, and α,β-unsaturated ketone groups. NMR data of 3 closely resembled those of felixin A (6)(ref. 6) (Fig. 1), except for an additional oxymethine signal (δ_C 68.4/δ_H 4.60, 1H, m, CH-6), consistent with a C-6 hydroxy substitution, further confirmed by ¹H–¹H COSY crosslations of H-5/H-6/H₂-7 (Fig. 6).

Fig. 6 Key COSY and HMBC correlations of 3.

In the NOESY spectrum of 3 (Fig. 7), a correlation between H-6 (δ_H 4.60) and H₃-21 (δ_H 1.24) placed the C-6 hydroxy group on the α-face. H-16 (δ_H 6.64) showed a correlation with H₃-25 (δ_H 2.34), consistent with an s-trans α,β-unsaturated ketone. The NOESY data of 3 were comparable to those of 2 and 6, indicating the same stereochemical framework, and the stereogenic centers of 3 were assigned as 5S, 6S, 8R, 9S, 10S, 12S, 13R, 14S.

Fig. 7 Stereo-view of 3 (generated by computer modeling) and calculated distances (Å) between selected protons with key NOESY correlations.

Compounds 1, 2, and 4 were evaluated for osteogenic activity in MG63 cells at 10 µM (72 h). Compound 1 enhanced ALP activity (20.04 KU per mgprot) and cell viability (159.90%), whereas compound 2 reduced viability to 30.02%. Compound 4 was the most cytotoxic, lowering viability to 14.64% (Table 2).

Table 2 The ALP activity was assessed after treating MG63 cells with homoscalaranes 1, 2, and 4 and alendronate sodium (positive control) at concentration of 10 µM for 72 h^a

Compounds	ALP activity (king unit per mgprot)	MTT (% control)
a Data are expressed with the mean standard error of the mean (SEM) (n = 3). The significance was determined with Student's t-test.b p < 0.01 and comparison with untreated cells.
1	20.04 ± 3.67^b	159.90 ± 2.28
2	3.81 ± 1.91	30.02 ± 1.75
4	−5.65 ± 0.79	14.64 ± 0.34
Alendronate sodium	21.45 ±± 5.21^b	95.14 ± 12.24
Control	2.53 ± 0.63	100.03 ± 2.28

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3 Conclusions

Marine sponges of the genus Lendenfeldia are well known as rich sources of scalarane-type sesterterpenoids with diverse structures and notable biological activities.^16,17 In this study, three new 24-homoscalaranes, lendenfeldaranes W–Y (1–3), along with a known analogue, lendenfeldarane D (4),⁹ were isolated from Lendenfeldia sp. In MG63 osteoblast-like cells, compound 1 significantly enhanced ALP activity and cell viability, showing effects comparable to or exceeding those of alendronate sodium, whereas compound 4 was cytotoxic and suppressed osteogenic differentiation. These results underscore the osteogenic potential of scalarane derivatives and support further investigation of sponge-derived sesterterpenoids as candidates for bone regenerative agents.

4 Experimental

4.1 General experimental procedures

Optical rotations were measured on a JASCO P-1010 digital polarimeter using the sodium D line (589 nm) with a 10 mm cell. IR spectra were obtained with a Thermo Scientific Nicolet iS5 FT-IR spectrophotometer. NMR spectra were recorded on a 600 MHz Jeol ECZ NMR spectrometer using the residual CHCl₃ (δ_H 7.26 ppm) and CDCl₃ (δ_C 77.0 ppm) as internal standards for ¹H and ¹³C NMR, respectively; coupling constants (J) are presented in Hertz (Hz). ESIMS and HRESIMS were acquired on a Thermo Fisher Orbitrap Exploris 120 (positive SI). Crude extracts were fractionated by silica gel CC (230–400 mesh, Merck). TLC was performed on silica gel 60F₂₅₄ (0.20 mm, Macherey-Nagel) and RP-18 F₂₅₄s (0.16–0.20 mm, Merck) plates, visualized under UV and with 10% H₂SO₄/heat. Final purification used RP-HPLC (Luna C18(2), 5 µm, 100 Å, 250 × 21.2 mm) on a Hitachi L-7110 pump with L-2400 PDA detector.

4.2 Animal material

A specimen of the genus Lendenfeldia was collected by SCUBA diving along the southern coast of Taiwan in April 2019. The material was preserved as a voucher (specimen no. 2019-04-SP) at the National Museum of Marine Biology & Aquarium (NMMBA), Taiwan. Species-level identification was confirmed by Professor Yusheng M. Huang (National Penghu University of Science and Technology).

4.3 Extraction and isolation

The freeze-dried sponge (wet/dry: 2900/213 g) was extracted with MeOH/CH₂Cl₂ (1 : 1, v/v) at room temperature. The crude extract (33.7 g) was partitioned between EtOAc and water, and the EtOAc layer (7.93 g) was fractionated by silical gel CC (n-hexane → n-hexane/EtOAC) to give 14 fractions (A–N). Fraction G was further purified by silica gel CC (n-hexane/acetone, 8 : 1 → acetone) to yield subfractions G1–G15, and G10 was subjected to RP-HPLC (C18, MeOH/H₂O 80 : 20, 5.0 mL min⁻¹) to afford 3 (0.7 mg, R_t = 20.9 min), 2 (1.6 mg, R_t = 39.1 min), 4 (1.0 mg, R_t = 47.4 min), and 1 (1.2 mg, R_t = 53.4 min), respectively.

4.3.1 Lendenfeldarane W (1). Amorphous powder; [α] −81 (c 0.09, CHCl₃); IR (KBr) ν_max 3419, 1735 cm⁻¹; ¹H (600 MHz, CDCl₃) and ¹³C NMR (150 MHz, CDCl₃) data see Table 1; ESIMS: m/z 499 [M + Na]⁺; HRESIMS: m/z 499.30284 (calcd for C₂₈H₄₄O₆ + Na, 499.30301).

4.3.2 Lendenfeldarane X (2). Amorphous powder; [α] 96 (c 0.08, CHCl₃); IR (KBr) ν_max 1738, 1682 cm⁻¹; ¹H (600 MHz, CDCl₃) and ¹³C NMR (150 MHz, CDCl₃) data see Table 1; ESIMS: m/z 509 [M + Na]⁺; HRESIMS: m/z 509.28714 (calcd for C₂₉H₄₂O₆ + Na, 509.28736).

4.3.3 Lendenfeldarane Y (3). Amorphous powder; [α] 162 (c 0.05, CHCl₃); IR (KBr) ν_max 3443, 1731, 1663 cm⁻¹; ¹H (600 MHz, CDCl₃) and ¹³C NMR (150 MHz, CDCl₃) data see Table 1; ESIMS: m/z 469 [M + Na]⁺; HRESIMS: m/z 469.29239 (calcd for C₂₇H₄₂O₅ + Na, 469.29245).

4.3.4 Lendenfeldarane D (4). Amorphous powder; [α] 135 (c 0.08, CHCl₃) (ref. 9 [α] 38 (c 0.05, CHCl₃)); IR (KBr) ν_max 1740, 1672 cm⁻¹; ESIMS: m/z 523 [M + Na]⁺.

4.4 ALP activity assay and cell viability assays

The osteogenic activity of compounds 1, 2, and 4 was evaluated in MG63 human osteoblast-like cells obtained from the Bioresource Collection and Research Center (BCRC, Hsinchu, Taiwan; BCRC 60279). ALP activity was measured following treatment with test compounds according to establish protocols with minor modifications.¹⁸ Cell viability was assessed by MTT assay: MG63 cells (1 × 10³ per well) were seeded in 96-well plates, incubated 24 h, and treated with alendronate (0.01 µM) or compounds (10 µM) for 72 h. MTT solution (10 µL, 5 mg mL⁻¹) and medium (90 µL) were added for 4 h, and formazan crystals were dissolved in 100 µL DMSO. Absorbance at 570 nm was measured as an indicator of viability.¹⁹

Author contributions

C.-Y. Huang, B.-R. Peng, Y.-W. Liu, Y.-Y. Chen, J.-H. Su, C.-C. Liaw, J.-J. Chen, C.-C. Tseng, Y.-J. Wu, Y.-B. Cheng, L. K. Tsou, M. M. Zhang, Z.-H. Wen: methodology, analysis, investigation, data curation, and draft preparation. L.-G. Zheng and P.-J. Sung: conceptualization, resources, supervision, project administration, visualization, draft review & editing, and funding acquisition.

Conflicts of interest

The authors declare no conflicts of interest.

Data availability

The datasets supporting this article have been uploaded as part of the supplementary information (SI). Supplementary information: HRESI-MS, 1D, and 2D-NMR spectra of 1–3. See DOI: https://doi.org/10.1039/d5ra07083j.

Acknowledgements

We thank Ms. Hsiao-Ching Yu and Ms. Chao-Lien Ho (High Valued Instrument Center, National Sun Yat-sen University) for assistance with MS (MS 006500) and NMR (NMR 001100) data acquisition under NSTC 113-2740-M-110-002. This work was partially supported by the National Museum of Marine Biology & Aquarium and NSTC, Taiwan, (grants NSTC 112-2320-B-291-002-MY3 and 114-2320-B-291-001), awarded to P.-J. Sung.

Notes and references

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