DOI: 10.1002/slct.202400274 ISSN: 2365-6549
An Efficient Biocatalytic Preparation of a Key Chiral Intermediate to the Anti‐Epileptic Drug Cenobamate Using an In‐House Recombinant Alcohol Dehydrogenase
Camille Assaf, Karolis Kurmis, Christopher Thomas Wimsey, Dwarampudi Adi Reddy, Mukesh Kumar Madhra, Matthew BycroftAbstract
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 %.