Creation of Asymmetric Catalysts Based on New Concept, and Their Application to Efficient Synthesis of Pharmaceutical Lead Compounds

我们开发了一种手性杂多金属配合物，包含镧系金属、碱金属和BINOL。该催化剂促进未修饰酮类和醛类具有高对映选择性的醛醇直接对映选择性反应。我们还开发了一种新的手性配体，连接BINOL，并发现锌配合物可以促进羟基酮和醛或亚胺之间非常有效的C-C键形成。催化剂的最大周转可达20000次，并保持了良好的对映体选择性。此外，我们开发了一种新的糖源催化剂，可以高效地促进酮类和酮亚胺的对映选择性氰硅化反应。利用这些催化剂，我们建立了喜树碱（抗癌药物）、奥昔布宁（毒蕈碱受体拮抗剂）和山茱萸醇（醛糖还原酶抑制剂）的高效合成路线。这些合成路线具有应用于工业合成的潜力。

We developed a chiral heteropolymetallic complex containing a lanthanide metal, alkali metal, and BINOL. This new catalyst promotes the direct enantioselective aldol reaction from unmodified ketones and aldehydes with high enantioselectivity. We also developed a novel chiral ligand, linked BINOL, and found that the zinc complex can promote very efficient C-C bond formation between a hydroxyl ketone and aldehydes or imines. The maximum catalyst turnover was reached up to 20000 with maintaining an excellent enantioselectivity. Moreover, we developed a new sugar-derived catalyst that can promote enantioselective cyanosilylation of ketones and ketoimines with high efficiency. Using these catalyses, we established efficient synthetic route of camptothecin (anticancer drug), oxybutynin (muscarinic receptor antagonist), and sorbinil (aldose reductase inhibitor). These synthetic route have a potential of being applied to industrial synthesis.