Development of highly efficient asymmetric synthesis process directed for "racemic switch" of the racemic medicines

开发针对外消旋药物“外消旋转换”的高效不对称合成工艺

基本信息

批准号：
16590084
负责人：
KUNIEDA Takehisa
金额：
$ 2.24万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The aim of this research is to establish the methodology for i) simple preparation of tricyclic "roofed" 2-oxazolidinones, 2-imidazolidinones and 2-thiazolidinones with conformational rigidity and steric congestion as extremely powerful chiral auxiliaries by catalytic resolution, and ii) excellent asymmetric reactions with bicyclic 2-amino alcohols, 1,2-diamines and 2-aminothiols derived from the above tricyclic compounds and their derivatives, directed for "racemic switch" of the racemic medicines.1.Easy access to highly efficient chiral auxiliaries by kinetic resolutionThe optically active "roofed" 2-oxazolidinones, 2-imidazolidinones and 2-thiazolidinones were readily obtained from kinetic resolution with oxazaborolidine catalysts.2.Application of highly efficient chiral "roofed" ligandsBicyclic "roofed" 2-amino alcohols, 1,2-diamines and 2-aminothiols derived from the corresponding tricyclic compounds have been proven to be good to excellent chiral ligands for following metal-catalyzed asymmetric reactions :(1)Asymmetric borane reduction of ketones with oxazaborolidine-borane system ("2-Aminoalcohol" ligands).(2)Practical synthesis of versatile chiral synthons, 4,5-dialkoxy-2-imidazolidinone ("2-Aminoalcohol" ligands).(3)Ruthenium (II)-catalyzed asymmetric transfer hydrogenation of ketones ("cis-1,2-Diamine" ligands).(4)Pd (II)-catalyzed asymmetric alkylation of allylacetates ("2-Aminothiol" ligands).(5)Cu (II)-catalyzed asymmetric Diels-Alder reaction ("2-Aminothiol" ligands).

本研究的目的是建立以下方法：i) 通过催化拆分简单制备具有构象刚性和空间拥挤性的三环“屋顶”2-恶唑烷酮、2-咪唑烷酮和 2-噻唑烷酮作为极其强大的手性助剂，以及 ii) 优异的手性助剂。与衍生自上述三环化合物的双环2-氨基醇、1,2-二胺和2-氨基硫醇的不对称反应及其衍生物，用于外消旋药物的“外消旋转换”。 1.通过动力学拆分轻松获得高效手性助剂光学活性“屋顶”2-恶唑烷酮、2-咪唑烷酮和2-噻唑烷酮可以通过动力学拆分轻松获得恶唑硼烷催化剂2.高效手性“屋顶”配体的应用双环“屋顶”2-氨基由相应的三环化合物衍生的醇、1,2-二胺和2-氨基硫醇已被证明是良好的手性配体，用于以下金属催化的不对称反应：（1）用恶唑硼烷-硼烷体系进行酮的不对称硼烷还原（“ 2-氨基醇”配体)。(2)多功能手性合成子的实用合成， 4,5-二烷氧基-2-咪唑啉酮（“2-氨基醇”配体）。(3)钌 (II) 催化的酮的不对称转移氢化（“顺式-1,2-二胺”配体）。(4)Pd ( II) 催化的乙酸烯丙酯（“2-氨基硫醇”配体）的不对称烷基化。(5)Cu (II)-催化的不对称狄尔斯-阿尔德反应（“2-氨基硫醇”配体）。