Development of General Methods for Preparation of Versatile Chiral Building Blocks and its Utilization for Syntheses of Biologically Active Compounds

由单烷基丙二酸和手性醇合成的手性半酯，在结晶诱导下发生不对称转化，只生成一种非对映异构体。因此，对映选择性地制备了具有三级立体中心的多功能手性结构单元，不对称1，3-丙二醇衍生物。利用手性结构单元的优势，对映选择性地合成了1 β-甲基碳青霉烯、依美替尼、原依美替尼、原依美替尼醇、tubulosine、二氢紫堇醇、二氢安替比林和二氢辛可宁，手性半酯在六甲基二硅氨基锂存在下的烷基化反应以非对映选择性方式构建了四级立体中心。从而为季铵型手性结构单元的合成提供了一种通用的合成方法。利用这一策略，α-烷基α-氨基酸和Hunteria和Aspidosperma型吲哚生物碱的光学纯的形式合成。此外，通过上述方法的应用，实现了具有氟原子的四元立体中心的对映选择性组装。

Chiral half esters, derived from monoalkymalonic acid and chiral alcohol, gave rise to the crystallization induced asymmetric transformation to afford exclusively one diastereoisomer. Thus, versatile chiral building blocks, unsymmetrical 1, 3-propanediol derivatives, having a tertiary stereogenic center, were enantioselectively prepared. Taking advantage of the chiral building blocks, 1beta-methylcarbapenem, emetine, protoemetine, protoemetinol, tubulosine, dihydrocorynantheol, dihydroantirhine and dihydrocinchonine were enentioselectively synthesized.Alkylation of the chiral half esters in the presence of lithium hexamethyldisilazide constructed the quaternary stereogenic center in a diastereoselective manner. Thus, a general synthetic method for the quaternary chiral building blocks has been developed. Exploiting this strategy, alpha-alkyl alpha-amino acids and Hunteria and Aspidosperma type indole alkaloids were synthesized in optically pure forms. Furthermore, the enantioselective assembly of quatemary stereogenic centers possessing a fluorine atom was achieved by the application of the above methodology.