The Synthesis of Deuterium, Carbon-14, and Carrier-Free Tritium Labeled Cannabinoids

Abstract

1′,2′‐Dehydroolivetol and its monomethyl ether, 5′‐bromoolivetol, and olivetol‐5,‐2H3, have been synthesized. Acid catalyzed condensation of the latter three compounds with p‐mentha‐2,8‐dien‐1‐ol gave 1′,2′‐dehydro‐Δ8‐THC methyl ether, 5′‐bromo‐Δ8‐THC, and Δ9‐THC‐5′‐2H3, respectively. 5′‐Bromo‐Δ8‐THC served as a precursor of 4′,5′‐dehydro‐Δ8‐ and Δ8‐THC, 4′‐ and 5′‐hydroxy‐Δ8‐THC, 5′‐dimethylamino‐Δ8‐THC and 5′‐carboxy‐Δ8‐THC. Reduction of 4′,5′‐dehydro‐Δ8‐ and Δ9‐THC in the presence of homogeneous catalysts afforded tritium labeled Δ8‐THC (50 Ci/mmole) and Δ9‐THC (58 Ci/mmole), respectively. Syntheses of Δ9‐THC‐11‐2H3, Δ9‐THC‐11‐14C cannabinol‐5,‐2H3′ and other labeled cannabinoids are described.