生物活性分子合成导向的外消旋吖丙啶不对称催化转化研究

具有重要生物活性手性分子的单一镜像异构体的高效精准合成是不对称催化发展的基本驱动力和目标之一。本项目申请拟以胺，醇，醛，烯醇硅醚等为亲核试剂，发展出路易斯酸催化外消旋2,2-二取代吖丙啶和/或2-（杂）芳基取代吖丙啶经由动力学拆分或对映汇聚式转化历程的不对称亲核开环反应体系，实现反应方法学上的突破。并以此为关键反应发展出新的高效合成路径来构建若干生物活性物质如氟康唑(FLC)类衍生物、神经激肽类NK1-拮抗剂Sch425078、β-取代的氨基丁酸类药物分子等的手性分子结构。

The efficient precise synthesis of a single enantiomer of chiral molecules bearing important bioactivities has been one of the fundamental driving forces and objectives of the development of asymmetric catalysis. The proposed project plans to achieve some methodological breakthroughs in employing amines, alcohols, aldehydes and enol ethers as nucleophiles to realize Lewis acid-catalyzed asymmetric nucleophilic ring openings of racemic 2,2-disubstituted and/or 2-(hetero)aryl aziridines via either kinetic resolution or enantioconvergent processes. With this method as the lynchpin reaction, novel synthetic routes would be established to access several bioactive molecules such as fluconazole derivatives, NK1 antagonist Sch425078 and β-substituted aminobutyric acids.