Highly efficient asymmetric synthesis process directed for optically pure medicines

针对光学纯药物的高效不对称合成工艺

基本信息

批准号：
13557196
负责人：
KUNIEDA Takehisa
金额：
$ 8.77万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
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 comformational 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.(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, which is an alternative method for optical resolution with "MAC-acid" (2-exo-methoxy-1-apocamphanecarboxylic acid).(2)Development of highly efficient chiral 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 :i)"2-Aminoalcohol" ligands :a)asymmetric borane reduction of ketones with oxazaborolidine-borane system.b)Practical synthesis of versatile chiral synthons, 4,5-dimethoxy-2-oxazolidinone and 4,5-demethoxy-2-imidazolidinone.c)asymmetric aldol reaction with Cu(II) catalyst.ii)"cis-1,2-Diamine" ligands :a)Ruthenium (II)-catalyzed asymmetric transfer hydrogenation of ketones.iii)"2-Aminothiol" ligands:a)Pd (II)-catalyzed asymmetric alkylation of allylacetates.b)Cu (II)-catalyzed asymmetric Diels-Alder reaction.

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) 优异的性能与衍生自上述的双环2-氨基醇、1,2-二胺和2-氨基硫醇的不对称反应(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-噻唑烷酮可以通过恶唑硼烷催化剂的动力学拆分轻松获得，这是一种替代方法用于使用“MAC-acid”（2-外切-甲氧基-1-阿朴莰甲酸）进行光学拆分(2)高效手性配体的开发由相应的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的优良手性配体不对称反应：i)“2-氨基醇”配体：a)用恶唑硼烷-硼烷对酮进行不对称硼烷还原系统.b)实用合成多功能手性合成子，4,5-二甲氧基-2-恶唑烷酮和4,5-去甲氧基-2-咪唑烷酮。c)与Cu(II)催化剂的不对称羟醛反应。ii)"cis-1, 2-二胺”配体：a)钌(II)催化的酮的不对称转移氢化。iii)“2-氨基硫醇”配体：a)Pd(II)催化的乙酸烯丙酯的不对称烷基化。b)Cu(II)催化的不对称Diels-Alder反应。