Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase

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-1 H -indene-4-carbonitrile could be completely converted into ( S )-1-((2-hydroxyethyl)amino)-2,3-dihydro-1 H -indene-4-carbonitrile in 70% isolated yield and >99% ee, demonstrating a great potential for the synthesis of the ozanimod intermediate in industrial applications.