Crassocolides A−F, Cembranoids with a trans-Fused Lactone from the Soft Coral Sarcophyton crassocaule

Abstract

Six new polyoxygenated cembrane-based diterpenoids possessing a trans-fused alpha-methylene-gamma-lactone, crassocolides A-F (1-6), have been isolated along with the known compound 7 from the ethyl acetate extract of a Taiwanese soft coral, Sarcophyton crassocaule. The structures of 1-6 have been established by detailed spectroscopic analysis, including 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY) spectroscopy, while their absolute configurations were determined using a modified Mosher's method for 1. The structure of 5 was further proven by X-ray diffraction analysis. The full assignment of NMR data of 7 is reported herein for the first time. The cytotoxicity of crassocolides 1-4, 6, and 7 against a limited panel of cancer cells was also determined.

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

“…crassocolide A, 24) were isolated from Sarcophyton crassocaule. [32] Crassolide A is cytotoxic against breast, liver, and lung cancer cell lines. [32] Many bioactive cembranolides have also been extracted from gorgonian octocorals of the genus Eunicea.…”

“…[32] Crassolide A is cytotoxic against breast, liver, and lung cancer cell lines. [32] Many bioactive cembranolides have also been extracted from gorgonian octocorals of the genus Eunicea. Particularly interesting from a biosynthetic viewpoint (see Section 4) is the cembranolide 25 which was isolated in 2006 from Eunicea mammosa and found to possess moderate cytotoxic activity against a panel of cell lines.…”

Cembrane Diterpenes Chemistry and Biological Properties

“…The soft coral of genus Sarcophyton are rich sources of cembranoid diterpenes, possessing an -methylidene--lactone moiety, including (+)-12-methoxycarbonyl-11Z-sarcophine (263) [13], trocheliophorol (264) [85], (7R,8S)-dihydroxydeepoxy-entsarcophine (265) [72], sarcocrassocolides A-E (266-270) [86], crassocolides A-F (271-276) [87], (-)-7 -hydroxy-8 -methoxydeepoxysarcophine (277) [88], 13-dehydroxysarcoglaucol-16-one, sarcoglaucol-16-one (278, 279) [89], 16-oxosarcoglaucol acetate (280) [8]. Among these compounds, compounds 266-269 were shown to exert significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells [86].…”

“…Among these compounds, compounds 266-269 were shown to exert significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells [86]. Crassocolide A (271) was cytotoxic against the four cancer cell lines, being significant (IC 50 3.1 μg/mL) to moderate (IC 50 8.6-11.9 μg/ mL) against Hep G2, and MCF-7, MDA-MB-231, and A549, respectively [87].…”

Achmatowicz reaction and its application in the syntheses of bioactive molecules

“…262-265 In particular, cembranolides bearing the α-methylene-γ-lactone substructure such as sinularolides, 266 crassocolides, 267, 268 michaolides, 269, 270 eupalmerins, 271 and uprolides 272-274 display potent cytotoxicity against various cancer cell lines. This may be due to their excellent Michael acceptor properties for biological nucleophiles.…”