Diastereoselective and Scalable Synthesis of 6-(S)-Hydroxycannabidivarin

Abstract

The synthesis of 6-(S)-hydroxycannabidivarin was required to assess its biological activity in the treatment of neurological disorders. A novel and scalable synthesis has been developed where the key step involves a Friedel−Crafts alkylation of phloroglucinol with (1S,2R,5R)-2-hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclohex-3-en-1-ylbenzoate. Careful optimization of the reaction conditions identified trifluoromethanesulfonic acid in isopropyl acetate as the best catalyst/solvent combination, providing optimum regioselectivity, diastereoselectivity, and yield for this step. This enabled the multigram synthesis of 6-(S)hydroxycannabidivarin in 10 steps from S-(+)-carvone.

Atropisomerism about aryl–C(sp3) bonds: chemically driven rotational pathway in cannabidiol derivatives

“…Therefore, there is a great need to develop chemical-synthetic strategies for CBD and its structural analogues (natural and synthetic). 2 a ,3 Moreover, among the numerous reported CBD analogues modification of the aromatic ring is limited to 3-hydroxyquinone moiety obtained by direct oxidation of the resorcinol ring. 3,4 Some quinone derivatives such as HU-331 and VCE-004.8 have shown potential for the development of new anticancer and neuroprotective agents, respectively.…”