文献类型：期刊文献

英文题名：Discovery of an Imine Reductase for Reductive Amination of Carbonyl Compounds with Sterically Challenging Amines

作者：Chen, Fei-Fei[1];He, Xue-Feng[1];Zhu, Xin-Xin[1];Zhang, Zhi[1];Shen, Xin-Yuan[1];Chen, Qi[1];Xu, Jian-He[1];Turner, Nicholas J.[2];Zheng, Gao-Wei[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Univ Manchester, Manchester Inst Biotechnol, Sch Chem, Manchester M1 7DN, England

年份：2023

卷号：145

期号：7

起止页码：4015

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20230513458635);WOS:【SCI-EXPANDED(收录号:WOS:000921362300001)】；

基金：ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (22008068 and 21878085) , the China Postdoctoral Science Foundation (2020M671027) , and the National Key Research and Development Program of China (2019YFA09005000 and 2021YFA0911400) . We thank Dr. Rui Liu and Prof. Guohua Liu of College of Chemistry and Materials Science of Shanghai Normal University for their kind assistance in chemical standard synthesis.

语种：英文

外文关键词：Carbonyl compounds - Nucleophiles - Substrates - Synthesis (chemical)

摘要：The synthesis of structurally diverse amines is of fundamental significance in the pharmaceutical industry due to the ubiquitous presence of amine motifs in biologically active molecules. Biocatalytic reductive amination for amine production has attracted great interest owing to its synthetic advantages. Herein, we report the direct synthesis of a wide range of sterically demanding secondary amines, including several important active pharmaceutical ingredients and pharmaceutical intermediates, via reductive amination of carbonyl substrates and bulky amine nucleophiles employing imine reductases. Key to success for this route is the identification of an imine reductase from Penicillium camemberti with unusual substrate specificity and its further engineering, which empowered the accommodation of a broad range of sterically demanding amine nucleophiles encompassing linear alkyl and (hetero)aromatic (oxy)alkyl substituents and the formation of final amine products with up to >99% conversion. The practical utility of the biocatalytic route has been demonstrated by its application in the preparative synthesis of the anti-hyperparathyroidism drug cinacalcet.