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

在β-碳原子上连接有杂原子的光学活性α-氨基酸不仅作为许多生物活性肽的组分而且作为合成有用化合物的手性结构单元是重要的。本研究中，作者发展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.β-庚烯基-α-乙酰胺基丙烯酸酯的立体选择性合成由相应的β-酮基-α-乙酰胺基丙烯酸酯合成了在β-位带有杂取代基的α-乙酰胺基丙烯酸酯。两种几何异构体都可以以完美的立体选择性制备。2.β-庚基-α-乙酰胺基丙烯酸酯的催化不对称氢化。由此获得的β-杂-α-乙酰胺基丙烯酸酯在具有反式螯合手性双膦TRAP的手性铑催化剂下以高对映选择性（高达97%ee）氢化，该催化剂是作者开发的。分别以（E）-和（Z）-底物为底物，以完全的立体特异性和高的对映选择性合成了苏型和赤型β-杂-α-氨基酸.环状β-庚烯基-α-氨基酸的催化不对称合成TRAP-铑催化剂对四氢吡嗪-2-甲酰胺的不对称氢化也是有效的，产生高达97%ee的（S）-哌嗪-2-（N-叔丁基）甲酰胺，其对于HIV蛋白酶抑制剂Crixivan的合成是重要的。有趣的是，这两种具有高对映体过量的对映体是可能的，由一个单一的手性源衍生的两个手性催化剂。

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.