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衍生的手性半酯引起结晶诱导的不对称转化，只得到一个非对映异构体。因此，具有三级立体生成中心的不对称1，3-丙二醇衍生物是一种多功能的手性构筑块，具有对映选择性。利用手性结构单元1β-甲基碳青霉烯、依米汀、原甲酸乙酯、原甲硫醇、微管糖苷、二氢骆驼蓬碱、二氢防己香碱和二氢辛可宁等手性化合物，在六甲基二硅氮化锂存在下进行烷基化反应，以非对映选择性方式构建了四元立体合成中心。因此，发展了一种通用的四元手性构筑块的合成方法。利用这一策略，以光学纯的形式合成了α-烷基-α-氨基酸和亨特瑞亚型和隐孢子型吲哚生物碱。此外，应用上述方法实现了含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.