亚胺还原酶催化的1-杂芳基四氢异喹啉的对映发散合成
Enantiodivergent Synthesis of 1-Heteroaryl Tetrahydroisoquinolines Catalyzed by Imine Reductases.
作者信息
Liu Tingting, Xu Zefei, Feng Jinhui, Yu Shanshan, Wang Min, Yao Peiyuan, Wu Qiaqing, Zhu Dunming
机构信息
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
National Center of Technology Innovation for Synthetic Biology, National Engineering Research Center of Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 Xi Qi Dao, Tianjin Airport Economic Area, Tianjin 300308, China.
出版信息
Org Lett. 2023 Apr 14;25(14):2438-2443. doi: 10.1021/acs.orglett.3c00603. Epub 2023 Apr 3.
Two enantiocomplementary imine reductases (IREDs) with high enantioselectivity were identified with catalytic activity toward the reduction of 1-heteroaryl dihydroisoquinolines through a screening of wild-type IREDs and enzyme engineering. Furthermore, ()-IR141-L172M/Y267F and ()-IR40 were applied to access a series of different 1-heteroaryl tetrahydroisoquinolines with high to excellent ee values (82 to >99%) and isolated yields (80 to 94%), thereby providing an effective method to construct this class of pharmaceutically important alkaloids, such as the intermediate of kinase inhibitor TAK-981.
通过对野生型亚胺还原酶（IREDs）的筛选和酶工程，鉴定出两种对1-杂芳基二氢异喹啉还原具有高对映选择性的对映互补IREDs。此外，（）-IR141-L172M/Y267F和（）-IR40被用于制备一系列不同的1-杂芳基四氢异喹啉，其对映体过量值（ee值）高至优异（82%至>99%），分离产率为80%至94%，从而提供了一种构建这类具有药学重要性的生物碱的有效方法，例如激酶抑制剂TAK-981的中间体。
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