Development of Catalytic Asymmetric Synthesis of Optically Active beta-Hetero-alpha-amino Acids

光学活性β-杂-α-氨基酸的催化不对称合成研究进展

基本信息

批准号：
09650935
负责人：
KUWANO Ryoichi
金额：
$ 0.7万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09650935/
关键词：
Catalytic Asymmetric Synthesis alpha-Amino Acid beta-Hydroxy-alpha-amino Acid alpha, beta-Diamino Acid Piperazine-2-carboxylic Acid Optically Active Compound Rhodium Catalyst Chiral Diphosphine Ligand 不斉水素化 α,β-ジアミノ酸不斉アリル化パラジウム触媒 /

项目摘要

Optically active alpha-amino acids attached a hetero atom on the beta-carbon atom are important as not only constituents of many biologically active peptides but also chiral building blocks for syntheses of useful compounds. In this study, the author developed some new catalytic asymmetric syntheses of optically active beta-hetero-alpha-amino acids.1. Stereoselective Synthesis of beta-Hetero-alpha-acetamldoacrylates. alpha-Acetamidoacrylates bearing a heterosubstituent at the beta-position were synthesized from the corresponding beta-keto-alpha- acetamidoacrylates. Both of the geometrical isomers were possible to be prepared with perfect stetreoselectivity.2. Catalytic Asymmetric Hydrogenation of beta-Hetero-alpha-acetamidoacrylates. The beta-hetero-alpha- acetamidoacrylates thus obtained were hydrogenated with high enantioselectivity (up to 97% ee) by a chiral rhodium catalyst possessing a trans-chelating chiral diphosphine TRAP, which had been developed by the authors. threo- and erythro-beta-Hetero-alpha-amino acids were obtained with complete stereospecificity and high enantioselectivity from the (E)- and (Z)-substrates, respectively.3. Catalytic Asymmetric Synthesis of Cyclic beta-Hetero-alpha-amino acids. The TRAP-rhodium catalysts were also effective for asymmetric hydrogenations of tetrahydropyrazine-2-carboxamides, giving (S)-piperazine-2-(N-tert-butyl)carboxamides with up to 97% ee, which are important for the synthesis of HIV protease inhibitor Crixivan. Of interest is that both of the enantiomers with high enantiomeric excess were possible to be obtained by two chiral catalysts derived from a single chiral source.

在β-碳原子上附着异质原子的光学活性α-氨基酸很重要，因为不仅许多生物活性肽的成分，而且是手性化合物合成的手性构建块。在这项研究中，作者开发了一些新的催化性不对称合成，这些合成器是光学活性β-源α-氨基酸的。1。 Beta-horpha-Alpha-Acetamldoacrylates的立体选择性合成。从相应的β-酮 - 甲状腺乙酰氨基丙烯酸酯中合成了β-位置上带有异卵的α-乙酰氨基丙烯酸酯。两种几何异构体都可以通过完美的稳定性制备2。 β-源性α-乙酰氨基丙烯酸酯的催化不对称氢化。这样获得的β型脑丙二酰胺丙烯酸酯是通过具有反内谢尔性手性迪磷脂陷阱的手性阳极催化剂的高对映选择性（高达97％EE）氢化的，该催化剂是由作者开发的。分别从（E） - 和（Z） - s-substrates.3中获得了完全的立体特异性和高的对映选择性，获得了threo-和reythro-beta-beta-hetero-alpha-氨基酸。3。环状β-型hetero-α-氨基酸的催化不对称合成。 TRAP-rHODIUM催化剂也对四氢吡嗪-2-羧化酰胺的不对称氢化也有效，给出了（S）-Piperazine-2-（N-TERT丁基）羧酰胺，最多为97％EE，这对于HIV蛋白酶抑制剂crixivan的合成很重要。有趣的是，两个具有高对映体过量的对映异构体可以通过一种源自单个手性源的手性催化剂来获得。