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Development of Synthetic Procedure of Physiologically Actlive Substances Using Asymmetric Synthesis Catalyzed by Peptide-Metal Complexes

肽-金属配合物催化不对称合成生理活性物质合成工艺的发展

基本信息

批准号：
05555245
负责人：
INOUE Shohei
金额：
$ 6.08万
依托单位：
Science University of Tokyo (1994)The University of Tokyo (1993)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

The present research is concerned with the asymmetric synthesis catalyzed by peptide-metal complexes with a peptide ligand whose amino terminal is modified by a Schiff base carrying a phenolic hydroxyl group. Asymmetric induction takes place by the participation of metal-peptide interaction in the reaction on the metai. Such an unprecedented approach made possible the successful asymmetric hydrocyanation of aldehyde (asymmetric cyanohydrin synthesis) with very high selectivitsy. Although this has not been possible except for enzymatic method, optically active cyanohydrins are very useful as intermediates for the stereoselective synthesis of physiologically active substances. The present method uses readily available amino acid as a catalyst component, and is expected to be practical. Peptide-metal complexes were found also effective for the asymmetric silylcyanation of aldehyde, asymmetric epoxidation of allyl alcohol, and asymmetric alkylation of aldehyde. The mechanism of these asymmetric inductions investigated by NMR studies afforded the guiding principle for the design of effective catalysts. AS an applicaiton of the asymmetric hydrocyanation of aldehyde, asymmetric cyanohydrin synthesis from beta-alkenylaldehyde followed by the highly stereoselective [3,3]sigmatropic chirality transfer was found to provide a facile synthesis of optically active gamma-cyanoallyl alcohol, which is useful as synthetic intermediate for a variety of naturally occurring and physiologically active substances.

本研究涉及肽金属配合物催化的不对称合成，其中肽配体的氨基末端被带有酚羟基的Schiff碱修饰。不对称诱导通过金属-肽相互作用参与金属上的反应而发生。这种前所未有的方法使得以非常高的选择性成功地进行醛的不对称氢氰化（不对称氰醇合成）成为可能。尽管除了酶促方法之外，这是不可能的，但光学活性氰醇作为生理活性物质的立体选择性合成的中间体是非常有用的。本发明的方法使用容易获得的氨基酸作为催化剂组分，并且预期是实用的。发现肽金属配合物对醛的不对称甲硅烷基氰化、烯丙醇的不对称环氧化和醛的不对称烷基化也是有效的。这些不对称诱导的机理通过NMR研究提供了有效的催化剂设计的指导原则。作为醛的不对称氢氰化反应的一个应用，由β-烯醛不对称合成氰醇，然后进行高度立体选择性的[3，3] σ-转移手性转移，可以简便地合成光学活性的γ-氰基烯丙醇，它可用作多种天然物质和生理活性物质的合成中间体。