Structural and stereochemical studies of alpha-methylene-gamma-lactone-bearing cembrane diterpenoids from a south china sea soft coral Lobophytum crassum.

Four new alpha-methylene-gamma-lactone-bearing cembranoids, 20-acetylsinularolide B (6), presinularolide B (7), 3-dehydroxylpresinularolide B (8), and 3-dehydroxyl-20-acetylpresinularolide B (9), together with five known analogues, sinularolides B-E (1- 4) and 20-acetylsinularolide C (5), were isolated from a South China Sea soft coral Lobophytum crassum. Their structures and relative stereochemistry were established by a combination of detailed spectroscopic data analysis and chemical correlations. The structures of 1- 9 were further confirmed by an X-ray diffraction study on a single crystal of sinularolide B (1). The absolute configurations of sinularolide B (1) and presinularolide B (7) were determined by a novel solid-state CD/TDDFT approach and by a modified Mosher's method, respectively. This study also revealed that the coupling constant between the lactonic methine protons ((3) J 1,2) varies considerably with different functional groups on the cembrane ring and that the determination of the stereochemistry of lactone ring fusion based on this coupling constant is risky. In a bioassay, sinularolides B and C (1 and 2) and new cembranoids 7 and 8 showed in vitro cytotoxicity against the tumor cell lines A-549 and P-388.