Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan .
Proc Jpn Acad Ser B Phys Biol Sci. 2006 Apr;82(2):72-85. doi: 10.2183/pjab.82.72.
Asymmetric catalysis is a powerful component of modern synthetic organic chemistry. To further broaden the scope and utility of asymmetric catalysis, new basic concepts for the design of asymmetric catalysts are crucial. Because most chemical reactions involve bond-formation between two substrates or moieties, high enantioselectivity and catalyst activity should be realized if an asymmetric catalyst can activate two reacting substrates simultaneously at defined positions. Thus, we proposed the concept of bifunctional asymmetric catalysis, which led us to the design of new asymmetric catalysts containing two functionalities (e.g. a Lewis acid and a Brønsted base or a Lewis acid and a Lewis base). These catalysts demonstrated broad reaction applicability with excellent substrate generality. Using our catalytic asymmetric reactions as keys steps, efficient total syntheses of pharmaceuticals and their biologically active lead natural products were achieved.
不对称催化是现代合成有机化学的重要组成部分。为了进一步拓宽不对称催化的范围和应用,设计不对称催化剂的新概念至关重要。由于大多数化学反应涉及两个底物或部分之间的键形成,如果不对称催化剂能够同时在确定的位置激活两个反应底物,则应该实现高对映选择性和催化剂活性。因此,我们提出了双功能不对称催化的概念,这导致我们设计了含有两种官能团的新型不对称催化剂(例如,路易斯酸和布朗斯台德碱或路易斯酸和路易斯碱)。这些催化剂表现出广泛的反应适用性和优异的底物通用性。使用我们的催化不对称反应作为关键步骤,实现了药物及其生物活性先导天然产物的有效全合成。