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

本文研究了氨基末端带有酚羟基的席夫碱修饰的多肽金属络合物催化的不对称合成。不对称诱导是通过金属-多肽相互作用参与金属上的反应而发生的。这种史无前例的方法使得醛的不对称氢氰化(不对称氰醇合成)具有非常高的选择性成为可能。虽然这是不可能的，除非酶方法，光学活性氰醇是非常有用的中间体，以立体选择性合成生理活性物质。本方法使用易得的氨基酸作为催化剂组分，有望实现实用。多肽-金属络合物对醛的不对称硅氰化反应、烯丙醇的不对称环氧化反应和醛的不对称烷基化反应也是有效的。核磁共振研究这些不对称诱导的机理为设计有效的催化剂提供了指导原则。作为醛的不对称氢氰化反应的一种应用，由β-烯醛合成不对称氰醇，然后进行高立体选择性的[3，3]手性转移，提供了一种简便的合成旋光活性的伽马氰基烯丙醇的方法，可作为合成多种天然存在的生理活性物质的中间体。

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.