NAD(P)H依赖型氧化还原酶不对称还原胺化制备手性胺的研究进展

NAD(P)H-dependent oxidoreductases for synthesis of chiral amines by asymmetric reductive amination of ketones

摘要:

不对称还原胺化反应是制备医药中间体手性胺结构单元的重要反应。目前已有许多不同种类的酶被应用于合成手性胺，其中NAD(P)H依赖型氧化还原酶催化的还原胺化反应最为引人注目，因为其能够一步将潜手性酮化合物完全转化为光学纯的手性胺化合物。文中以亚胺还原酶、氨基酸脱氢酶、冠瘿碱脱氢酶和还原性酮胺化酶为例，从NAD(P)H依赖型氧化还原酶的结构特征、作用机理、分子改造及催化应用等方面，综述了其在不对称还原胺化合成手性胺领域的研究进展。

Abstract:

Asymmetric reductive amination is one of the most important reactions in the preparation of chiral amine pharmaceutical intermediates. Different kinds of enzymes have been applied to the synthesis of chiral amines Among them, the development of reductive amination reactions catalyzed by NAD(P)H-dependent oxidoreductases is attractive, as it would permit a one-step transformation of prochiral ketones into chiral amines with high optical purity. In this review, the recent advances in enzyme structure, catalytic mechanism, protein engineering and the application in reductive amination reactions of NAD(P)H-dependent oxidoreductases, including imine reductase, amino acid dehydrogenase, opine dehydrogenase and reductive aminase, are summarized.