Elsevier

Tetrahedron

Volume 76, Issue 50, 11 December 2020, 131697
Tetrahedron

Four homoverrucosane-type diterpenes from the marine sponge Halichondria sp

https://doi.org/10.1016/j.tet.2020.131697Get rights and content

Highlights

  • Four new homoverrucosane-type diterpenes (1–4), were isolated from the marine sponge Halichondria sp.

  • The absolute configurations of 1–4 were determined by spectral analysis and theoretical calculation.

  • It was the first report that homoverrucosanes isolated from the marine sponge Halichondria sp.

Abstract

Four new homoverrucosane-type diterpenes (14) and two known analogs (56) were isolated from the marine sponge Halichondria sp. Their structures including absolute configurations were determined by combination of spectroscopic analyses, theoretical calculations and comparison with data of literatures. The cytotoxicity against human multiple myeloma cell line RPMI-8266 of compounds 14 was evaluated, but none showed activity (IC50 > 10 μM). It was the first report that homoverrucosanes isolated from the marine sponge Halichondria sp.

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 14 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 (14) 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 14 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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