Side chain methyl analogues of Δ8-THC

Article abstract of DOI:10.1016/S0040-4020(96)01134-9

The synthesis of both side chain epimers of 1'- (4), 2'- (5), 3'-methyl- (6) and 4'-methyl-Δ⁸-tetrahydrocannobinol (7) has been carried out. The synthetic approach entailed the acid catalyzed condensation of the appropriate substituted resorcinol with menthadienol to provide the Δ⁸-THC analogue. Both isomers of 1'- (4) and 2'-Δ⁸-THC (5) were more potent than Δ⁸-THC, both in vitro and in vivo. The 3'-methyl isomers (6) were approximately equal in potency to Δ⁸-THC, and 4'-methyl-Δ⁸-THC was less potent. There was relatively little difference in potency between the epimers of 4, 5, and 6.