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 ( Sc ADH), 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 %.