Artificial farnesol epoxidase enables a concise synthesis of meroterpenoids.

Abstract

Efficient asymmetric epoxidation reactions have been developed for both the head end and tail end double bonds of farnesol, greatly facilitating the synthesis of terpenoid natural products. However, the lack of methods for direct asymmetric epoxidation of the relatively inert internal alkene of farnesol has posed major challenges in the synthesis of many terpenoids. In this study, we describe the engineering of an epoxidase capable of selectively epoxidizing the internal alkene of farnesol with high regioselectivity and enantioselectivity. The resulting epoxidized intermediate has been successfully applied to simplify the synthesis of a variety of meroterpenoids, reducing the total number of synthetic steps by more than half in most cases.