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

Area of Science:

• Biocatalysis
• Organic Synthesis
• Medicinal Chemistry

Background:

• Efinaconazole is a key antifungal agent.
• Traditional synthesis methods can be environmentally taxing.
• Greener synthetic routes are highly desirable in pharmaceutical manufacturing.

Purpose of the Study:

• To develop an eco-friendly biocatalytic method for synthesizing efinaconazole.
• To utilize benzaldehyde lyase (BAL) for a key synthetic step.
• To establish an efficient and scalable production process.

Main Methods:

• Employed benzaldehyde lyase (BAL) to catalyze the benzoin condensation.
• Used 2,4-difluorobenzaldehyde as a substrate.
• Incorporated thiamin-diphosphate (ThDP) and Mg2+ as cofactors.

Main Results:

• Successfully synthesized the α-hydroxy ketone precursor biocatalytically.
• Developed a novel route to efinaconazole (7).
• Achieved a moderate overall yield of 38% for efinaconazole.

Conclusions:

• The biocatalytic approach offers a greener alternative to chemical synthesis.
• This method presents significant advantages over traditional chemical processes.
• Efficient and scalable procedures were established for efinaconazole production.