General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors: Enantioselective Total Syntheses of (+)- and (鈭?-Gliocladine C, (+)-Leptosin D, (+)-T988C, (+)-Bionectin A, a

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• 作者：John E. DeLorbe ; David Horne ; Richard Jove ; Steven M. Mennen ; Sangkil Nam ; Fang-Li Zhang ; Larry E. Overman
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：March 13, 2013
• 年：2013
• 卷：135
• 期：10
• 页码：4117-4128
• 全文大小：849K
• 年卷期：v.135,no.10(March 13, 2013)
• ISSN：1520-5126

文摘

A common strategy for preparing tryptophan-derived epidithiodioxopiperazine (ETP) natural products containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter is reported. This strategy is exemplified by enantioselective total syntheses of four heptacyclic ETP natural products鈥攇liocladine C (6), leptosin D (7), T988C (8), and bionectin A (9)鈥攕tarting with the di-(tert-butoxycarbonyl) derivative 17 of the trioxopiperazine natural product gliocladin C, which is readily available by enantioselective chemical synthesis. In addition, total syntheses of the enantiomer of gliocladine C (ent-6) and gliocladin A (11), the di(methylthio) congener of bionectin A, are reported. These syntheses illustrate a synthetic strategy wherein diversity in the dioxopiperazine unit of ETP natural products is introduced at a late stage in a synthetic sequence. In vitro cytotoxicity of compounds in this series against invasive human prostrate (DU145) and melanoma (A2058) cancer cell lines is described and compared to that of chaetocin A (4).