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,‐ 2 H 3 , have been synthesized. Acid catalyzed condensation of the latter three compounds with p ‐mentha‐2,8‐dien‐1‐ol gave 1′,2′‐dehydro‐Δ 8 ‐THC methyl ether, 5′‐bromo‐Δ 8 ‐THC, and Δ 9 ‐THC‐5′‐ 2 H 3 , respectively. 5′‐Bromo‐Δ 8 ‐THC served as a precursor of 4′,5′‐dehydro‐Δ 8 ‐ and Δ 8 ‐THC, 4′‐ and 5′‐hydroxy‐Δ 8 ‐THC, 5′‐dimethylamino‐Δ 8 ‐THC and 5′‐carboxy‐Δ 8 ‐THC. Reduction of 4′,5′‐dehydro‐Δ 8 ‐ and Δ 9 ‐THC in the presence of homogeneous catalysts afforded tritium labeled Δ 8 ‐THC (50 Ci/mmole) and Δ 9 ‐THC (58 Ci/mmole), respectively. Syntheses of Δ 9 ‐THC‐11‐ 2 H 3 , Δ 9 ‐THC‐11‐ 14 C cannabinol‐5,‐ 2 H 3 ′ and other labeled cannabinoids are described.