A pentacyclic hybrid cannabinoid (4) has been synthesized, which combines structural elements of traditional cannabinoids and cannabmimetic indoles. Cannabinoid 4 contains a 1-pentylindole structure fused to the 2,3-positions of the partially reduced hydroxydibenzopyran system of THC. The successful approach to 4 employed 9-benzoyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole (17) as the starting material. Dehydrogenation to carbazole 18, followed by demethylation and condensation with trans-p-menthadienol gave N-benzoyl hybrid cannabinoid 22, N-alkylation of which afforded target cannabinoid 4. The hybrid cannabinoid had affinity for the CB1 receptor approximately equal to that of Delta(8)-THC (K-i=19.3+/-3 nM), and shows comparable potency in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved
Synthesis and pharmacology of a hybrid cannabinoid
Huffman, JW., Lu, JZ., Dai, D., Kitaygorodskiy, A., Wiley, J., & Martin, BR. (2000). Synthesis and pharmacology of a hybrid cannabinoid. Bioorganic and Medicinal Chemistry, 8(2), 439-447.