Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines

A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which:displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, to 15 g L-1 1-Me DHIQ was converted: completely without a feeding strategy. Furthermore, the: reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields, (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).