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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一种方法，用于i）通过催化拆分简单制备具有构象刚性和空间拥挤的三环"屋顶" 2-恶唑烷酮，2-咪唑烷酮和2-噻唑烷酮作为非常强大的手性助剂，ii）与双环2-氨基醇，1，衍生自上述三环化合物的2-二胺和2-氨基硫醇及其衍生物，直接用于外消旋药物的"外消旋转换"。1.通过动力学拆分容易获得高效的手性助剂2.高效手性"屋顶"配体的应用由相应三环化合物衍生的双环"屋顶" 2-氨基醇、1，2-二胺和2-氨基硫醇已被证明是以下金属催化不对称反应的优良手性配体：（1）恶唑硼烷-硼烷体系（"2-氨基醇"配体）对酮的不对称硼烷还原。（2）多功能手性配体4，5-二烷氧基-2-咪唑啉酮（"2-氨基醇"配体）的合成。（3）钌（II）催化的酮（"顺式-1，2-二胺"配体）的不对称转移氢化。(4)Pd（II）乙酸烯丙酯（"2-氨基硫醇"配体）的催化的不对称烷基化。(5)Cu（II）催化的不对称Diels-Alder反应（“2-氨基硫醇”配体）。