Biotransformations with Imine Reductases: Design of a Practical Process Avoiding an Extractive Work-Up by Entrapment of Water and Enzymes in an Immobilized Phase

A process concept for the asymmetric biocatalytic reduction of heterocyclic imines addressing the efficiency of the reaction as well as downstream-processing steps was studied by utilizing a heterogenized aqueous phase, which contains the needed enzymes and cofactor within a superabsorber (polyacrylate) network, for the biotransformation. The immobilized biocatalytic system, which comprises an imine reductase (IRED), NADPH and an alcohol dehydrogenase for cofactor-recycling, enables to run the reaction in pure organic medium. Thus, instead of an extractive work-up as typical solution for biotransformations in aqueous medium, which, however, can be tedious due formation of emulsions, this type of IRED-catalyzed process leads to a simplified work-up consisting only of a decantation of the liquid organic reaction medium with the product from the heterogenized aqueous biocatalyst system. Exemplified for the (R)-enantioselective reduction of 1-methyl-3,4-dihydroisoquinoline by the IRED of Streptomyces viridochromogenes as a model reaction, a process was developed leading to 98 % conversion, 88 % yield and >99 % ee at a substrate concentration of 40 mM.

Automated summary

A process concept for the asymmetric biocatalytic reduction of heterocyclic imines was studied, which utilizes a heterogenized aqueous phase containing enzymes and cofactors for the biotransformation in pure organic medium. The process simplifies the work-up steps and achieves high conversion, yield, and enantiomeric excess.