A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield.

Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg resulted in the formation of α-hydroxy ketone which then underwent the preparation of . This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of in a moderate 38% yield.