title: General approach for preparing epidithiodioxopiperazines from trioxopiperazine precursors: enantioselective total syntheses of (+)- and (-)-gliocladine C, (+)-leptosin D, (+)-T988C, (+)-bionectin A, and (+)-gliocladin A.
abstract: 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).
authors: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
authors: John E
authors: JE
authors: DeLorbe
authors: David
authors: D
authors: Horne
authors: Richard
authors: R
authors: Jove
authors: Steven M
authors: SM
authors: Mennen
authors: Sangkil
authors: S
authors: Nam
authors: Fang-Li
authors: FL
authors: Zhang
authors: Larry E
authors: LE
authors: Overman
mesh_terms: D018360:Crystallography, X-Ray; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D026121:Indole Alkaloids; D010879:Piperazines; D011760:Pyrrolidinones; C497290:T988 C compound; C516593:bionectin A; C583099:epidithiodioxopiperazine; C583097:gliocladin A; C518056:gliocladin C; C583098:leptosin D