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.
Zhang
Wen
W
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Shanghai, 201203, People's Republic of China.
Krohn
Karsten
K
Ding
Jian
J
Miao
Ze-Hong
ZH
Zhou
Xiu-Hong
XH
Chen
Si-Han
SH
Pescitelli
Gennaro
G
Salvadori
Piero
P
Kurtan
Tibor
T
Guo
Yue-Wei
YW
D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D002681:China; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D009792:Oceans and Seas; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004224:Diterpenes; D007783:Lactones