Four homoverrucosane-type diterpenes from the marine sponge Halichondria sp
Graphical abstract
Introduction
Marine sponge Halichondria sp are well known to be a source of halicondrin B, which was the lead compound of anti-metastatic breast cancer drug eribulin mesylate (aka Halaven ®) [1]. In addition, Halichondria sp is also rich in other structurally-unique metabolites, including macrolides, terpenes, sphingolipid glycosides, sterols, alkaloids, lactams, etc. Biological activities of these metabolites such as anthelmintic, antimalarial, antimicrobial, and cytotoxic properties have also been reported in the previous literatures [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]]. Homoverrucosanes are a family of 7, 6, 5-tetracyclic diterpenes in the trans–anti–trans configuration, initially isolated in the liverworts Schistochila rigidula [14]. Later, some modified structures have also been found in other liverworts and marine sponges [[15], [16], [17], [18]].
In our continuing search for bioactive compounds from marine organisms, the yellow planar sponge Halichondria sp. was subjected to chemical study, whose EtOAc extract significant showed toxicity against brine shrimp. Further isolation yielded four new homoverrucosane derivatives: 2, 5-dihydroxy-homoverrucos-(3)-ene (1), 2-hydroxy-5-oxo-homoverrucos-(3)-ene (2), 5, 18-dihydroxy-homoverrucosane (3), 5-hydroxy-18-aldehyde-homoverrucosane (4), together with two known compounds: homoverrucosanol (5), neoverrucosanol (6) (Fig. 1). The human multiple myeloma cell line RPMI-8266 inhibitory activity of 1–4 were evaluated. Details of the structure elucidation, and bioactivity screening of these metabolites are reported herein.
Section snippets
Result and discussion
2, 5-dihydroxy-homoverrucos-(3)-ene (1) was obtained as a white solids. Its molecular formula was determined as C20H34O2 as established by HRESIMS (m/z 329.2458 [M + Na]+), requiring 4° of unsaturation. The IR spectrum exhibited absorptions for two hydroxy groups at 3450 and 3348 cm−1. The 1H NMR spectrum of 1 exhibited the presence of five methyls, two oxygenated methines at δH 3.73 (d, J = 7.5 Hz, H-2), 4.21 (m, H-5), and one olefinic methine at 5.61 (d, J = 3.7 Hz, H-4). The 13C NMR, DEPT
Conclusion
With the aim of discovering structurally novel compounds, four new homoverrucosane-type diterpenes (1–4) were isolated from the marine sponge Halichondria sp. Their structures including absolute configurations were determined by a combination of spectroscopic analyses, theoretical calculations and comparison with data of literatures. Homoverrucosane-type diterpenes were originally isolated from plants, which are very rare in sponges. Compounds 1–4 were evaluated for their activities against
General experimental procedures
Optical rotation measurements were conducted on an Autopol I polarimeter (No. 30575, Rudolph Research Analytical) with a 10 cm length cell at room temperature. UV and IR (KBr) spectra were recorded on a Hitachi U-3010 spectrophotometer and Jasco FTIR-400 spectrometer, respectively. CD spectra were obtained on a Jasco J-715 spectropolarimeter. 1H, 13C, DEPT-135, COSY, HSQC, HMBC, and NOESY NMR spectra were recorded at room temperature on a Bruker Avance DRX-600 MHz (or 500 MHz) NMR spectrometer.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was financially supported by the Natural Science Foundation of Fujian Province of China (Grant No: 2019J05032).
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