文章基本信息

标题：Total synthesis of (±)-halichlorine, (±)-pinnaic acid, and (±)-tauropinnaic acid
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作者：Hamish S. Christie ; Clayton H. Heathcock
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：33
页码：12079-12084
DOI：10.1073/pnas.0403887101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The related marine natural products halichlorine, pinnaic acid, and tauropinnaic acid have been synthesized. The described route provided access to all three compounds from a common, late-stage intermediate. The synthesis began with 1-pyrrolidino-1-cyclopentene from which an intermediate possessing the three contiguous stereocenters of the natural products was synthesized in just four steps. Olefin cross metathesis followed by a hydrogenation/hydrogenolysis reaction stereoselectively formed the piperidine ring. Use of a {beta}-lactam group provided internal protection for the highly congested nitrogen atom during side-chain elaboration. The {beta}-lactam was subsequently reduced directly to an amino aldehyde, which after the Horner-Wadsworth-Emmons reaction was elaborated to pinnaic acid. The same amino aldehyde was also transformed into halichlorine after a thiol-mediated cyclization sequence to form the dehydroquinolizidine ring system.