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-碳原子上连接杂原子的光学活性 α-氨基酸不仅作为许多生物活性肽的成分而且作为用于合成有用化合物的手性结构单元很重要。在本研究中，作者开发了一些新的催化不对称合成光学活性β-杂-α-氨基酸的方法。 1． β-杂-α-乙酰氨基丙烯酸酯的立体选择性合成。由相应的β-酮基-α-乙酰氨基丙烯酸酯合成在β位带有杂取代基的α-乙酰氨基丙烯酸酯。两种几何异构体均具有良好的立体选择性。 2． β-杂-α-乙酰氨基丙烯酸酯的催化不对称氢化。由此获得的β-杂-α-乙酰氨基丙烯酸酯通过作者开发的具有反式螯合手性二膦TRAP的手性铑催化剂进行高对映选择性（高达97％ee）的氢化。分别从(E)-和(Z)-底物中获得了具有完全立体特异性和高对映选择性的苏式-和赤式-β-杂-α-氨基酸。3．环状β-杂-α-氨基酸的催化不对称合成。 TRAP-铑催化剂对于四氢吡嗪-2-甲酰胺的不对称氢化也很有效，得到的(S)-哌嗪-2-(N-叔丁基)甲酰胺的ee高达97%，这对于HIV的合成很重要蛋白酶抑制剂 Crixivan。有趣的是，两种具有高对映体过量的对映体都可以通过源自单一手性源的两种手性催化剂获得。