Abstract
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, (R)-IR141-L172M/Y267F and (S)-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.
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