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Diastereoselective and Scalable Synthesis of 6-(S)-Hydroxycannabidivarin
Hannah V Stone1, Frederick J Topping1, Alberte X Veiga1
1Discovery and Medicinal Chemistry Department, Jazz Pharmaceuticals Inc., Building 735, Kent Science Park, Sittingbourne ME9 8AG, U.K.
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.
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