Cannabidiol as the Substrate in Acid-Catalyzed Intramolecular Cyclization

Abstract The chemical reactivity of cannabidiol is based on its ability to undergo intramolecular cyclization driven by the addition of a phenolic group to one of its two double bonds. The main products of this cyclization are Δ9-THC (trans-Δ-9-tetrahydrocannabinol) and Δ8-THC (trans-Δ-8-tetrahydrocannabinol). These two cannabinoids are isomers, and the first one is a frequently investigated psychoactive compound and pharmaceutical agent. The isomers Δ8–iso-THC (trans-Δ-8-iso-tetrahydrocannabinol) and Δ4(8)–iso-THC (trans-Δ-4,8-iso-tetrahydrocannabinol) have been identified as additional products of intramolecular cyclization. The use of Lewis