A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield
Zhiran Ju, Zhiyun Li, Menglan Li, Saili Xu, Kumaravel Kaliaperumal, Fen‐Er Chen
Abstract
Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole ( 7 ), 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 2+ resulted in the formation of α-hydroxy ketone which then underwent the preparation of 7 . 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 7 in a moderate 38% yield.