Toward an environmentally friendly synthesis of chiral γ-lactones: A biocatalytically oxidative desymmetrization pathway

Abstract

The direct use of oxygen for the enantioselective Baeyer–Villiger oxidation of cyclobutanone represents a promising, environmentally benign method of generating substituted chiral γ-lactones, a recurrent motif in natural product skeletons. We herein demonstrate a highly efficient process for the desymmetrization of cyclobutanones by a Baeyer–Villiger monooxygenase that originated from Acinetobacter radioresistens (ArBVMO). By coupling a formate dehydrogenase to the monooxygenase, the reaction can readily be performed at high substrate loading (200 mM) in buffer/toluene biphasic systems. Scaling up the reaction led to bioconversion with a space-time yield of up to 115 g L−1 day−1, and perfect enantioselectivity (> 99% ee). The discovery of ArBVMO provides a practical synthetic route to γ-lactones, overcoming the problems of poor accessibility and the high cost of waste disposal incurred by previous methodologies.