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Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase
Jinyang Li1,2, Zefei Xu2, Jinhui Feng2
1School of Biotechnology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin 300457, China.
Abstract:
Asymmetric synthesis of chiral N-hydroxyethyl amino indane derivatives remains challenging. In this study, an imine reductase mutant (IR262-F185E/F229L) was identified with high enantioselectivity toward various N-hydroxyethyl imino derivatives. Furthermore, a continuous fed-batch strategy was designed to avoid the hydrolysis of imines, and up to 200 mM 1-((2-hydroxyethyl)imino)-2,3-dihydro-1H-indene-4-carbonitrile could be completely converted into (S)-1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-indene-4-carbonitrile in 70% isolated yield and >99% ee, demonstrating a great potential for the synthesis of the ozanimod intermediate in industrial applications.
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