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

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 (1 S ,2 R ,5 R )-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.