Veraguamides A鈭扜, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium Symploca cf. hydnoides from Guam

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• 作者：Lilibeth A. Salvador ; Jason S. Biggs ; Valerie J. Paul ; Hendrik Luesch
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：May 27, 2011
• 年：2011
• 卷：74
• 期：5
• 页码：917-927
• 全文大小：918K
• 年卷期：v.74,no.5(May 27, 2011)
• ISSN：1520-6025

文摘

Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A鈭扜 (1鈭?b>7), together with the known compound dolastatin 16. The planar structures of 1鈭?b>7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher鈥檚 analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A鈭扜 (1鈭?b>7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an 伪-hydroxy acid, and a C₈-polyketide-derived 尾-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure鈭抋ctivity relationship analysis identified several sensitive positions in the veraguamide scaffold that affect the cytotoxic activity of this compound class. Dolastatin 16 showed only weak cytotoxic activity on both cell lines tested. The complete stereostructure of dolastatin 16 was proposed for the first time through degradation followed by a combination of advanced Marfey鈥檚 analysis and modified Mosher鈥檚 analysis using phenylglycine methyl ester as a chiral anisotropic reagent.