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

被引：82

作者：

DeLorbe, John E. ^{[1
]}

Horne, David ^{[2
]}

Jove, Richard ^{[2
]}

Mennen, Steven M. ^{[1
]}

Nam, Sangkil ^{[2
]}

Zhang, Fang-Li ^{[1
]}

Overman, Larry E. ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

[2] City Hope Comprehens Canc Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 10期

关键词：

CIRCULAR-DICHROISM; GLIOTOXIN; METABOLITES; APOPTOSIS; CHAETOCIN; FUNGUS; INHIBITOR; CHEMISTRY; AGENT; 2,5-DIKETOPIPERAZINES;

D O I：

10.1021/ja400315y

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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-gliocladine C (6), leptosin D (7), T988C (8), and bionectin A (9)-starting 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).

引用

页码：4117 / 4128

页数：12

共 61 条

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