An Efficient Biocatalytic Preparation of a Key Chiral Intermediate to the Anti‐Epileptic Drug Cenobamate Using an In‐House Recombinant Alcohol Dehydrogenase

In this investigation, the preparation of the chiral intermediate, (R)‐1‐(2‐chlorophenyl)‐2‐(2 H‐tetrazol‐2‐yl)ethan‐1‐ol (2 a), a precursor to the anti‐epileptic drug Cenobamate, was demonstrated using a very efficient alcohol dehydrogenase (ADH) enzyme from a simple ketone substrate. The enzyme, ADH107604 from Streptomyces coelicolor (ScADH), identified from Dr. Reddy's in‐house collection of biocatalysts, showed excellent activity against the ketone 1‐(2‐chlorophenyl)‐2‐(2 H‐tetrazol‐2‐yl)ethan‐1‐one 1, and the (R)‐alcohol product 2 a was obtained with excellent conversion and enantiomeric excess (ee) >99 %. A valuable alcohol intermediate to the anti‐epileptic drug Cenobamate is prepared using a recombinant alcohol dehydrogenase from Streptomyces coelicolor. This enzymatic process provides a simple and green procedure, compared to an asymmetric hydrogenation route, with the (R)‐alcohol product obtained with excellent conversion and enantiomeric excess >99 %.