Bromination of Cannabinoids from Cannabis sativa L.: A Comparative Study Using an Enzymatic Catalysis Approach.

An in-depth study on bromination of six typical cannabinoids from Cannabis sativa L. is reported using three different methods: micellar-assisted enzymatic catalysis, NBS, and Oxone. Under the micelle-enabled CiVCPO-catalyzed conditions, selective dibromination of cannabinoids was achieved in up to 72% isolated yield for CBN and 67% for CBL with complete substrate conversion. Notably, the bromination level could be tuned by varying enzyme concentration (300-500 nM), enabling controlled access to mono- or dibrominated products. Compared to conventional methods, the enzymatic system demonstrated comparable or superior efficiency while avoiding overoxidation and enabling improved selectivity. This work highlights a mild and selective strategy for the late-stage functionalization of sensitive natural products, providing a promising platform for the development of bioactive cannabinoid derivatives.