Beta-硝基醇是一类重要的有机分子，可用于合成其它有用结构，例如beta-氨基醇。后者是众多药物分子的必要结构组成，也被广泛用作手性配体和辅基。本课题拟采用羰基还原酶来不对称还原alpha-硝基酮从而制备手性beta-硝基醇。为了考察酶还原反应的电子和位阻效应，优化的催化体系将被用于羰基连有不同基团的底物的还原。采用动态动力学拆分的策略，我们也将研究alpha-碳含烷基取代基的alpha-硝基酮的不对称酶还原，有望高产率、高立体选择性地合成含两个手性中心的beta-硝基醇。本课题发展的方法将被用于beta-氨基醇类药物去甲伪麻黄碱、地诺帕明以及anacetrapib关键中间体的高效化学酶法合成。本研究将拓宽羰基还原酶的底物范围，为其分子作用机理提供重要信息。申请人在有机合成和酶催化领域具有的丰富研究经验，以及所在团队和依托单位具有的强大研究实力与完善仪器设备都将是达到研究目标的重要保证。

Beta-nitro alcohol is an important class of organic molecules, which can be used for synthesis of other useful structures, such as beta-amino alcohol. The latter is not only the essential structural component of many pharmaceuticals, but also widely used as chiral ligands and auxiliaries. Our program aims to prepare chiral beta-nitro alcohols through ketoreducatse catalyzed asymmetric reduction of alpha-nitro ketones. To examine the electronic and steric effects, the optimized catalytic system will be applied to the reduction of a series of substrates with different groups attaching to the carbonyl group. Using a dynamic kinetic resolution strategy, we will also study the asymmetric enzymatic reduction of alpha-nitro ketones with an alkyl substitute at the alpha-carbon, hoping to efficiently generate beta-nitro alcohols with two stereogenic centers in a highly stereoselective manner. The developed method will be applied to the efficient chemo-enzymatic synthesis of norpseudoephedrine, denopamine and the key intermediate of anacetrapib, which all belong to the beta-amino alcohol family of pharmaceuticals. Our proposed research will not only expand the substrate scope of ketoreducatse, but also provide important information for the enzyme mechanism. It is believed that the proposed research goals will be realized because of the applicant’s good research experience in organic synthesis and enzyme catalysis, as well as the great research facilities belonging to the research team and its affiliated department.