Stereoselective Synthesis of the Epimeric Δ7-Tetrahydrocannabinols
Both C9 epimers of Δ7-THC (3 and 4) have been synthesized from Δ8-THC methyl ether (12). Hydroboration of 12 gave a mixture of stereoisomeric 8-hydroxyhexahydrocannabinols. The 8α-ol was converted into the 9β-methyl epimer (4) of Δ7-THC, while the 8β-ol was converted into 3. Molecular modeling indicated that 4 should have significant cannabinoid activity, while 3 was predicted to be weakly active. These predictions were borne out by both in vitro and in vivo pharmacology.
Huffman JW, Kenneth Banner W, Zoorob GK, Howard Joyner H, Reggio PH, Martin BR, Compton DR. 1995. Stereoselective synthesis of the epimeric Δ7-tetrahydrocannabinols. Tetrahedron 51(4):1017-32.