Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
, 39 (19), 3790-6

Unsaturated Side Chain beta-11-hydroxyhexahydrocannabinol Analogs

Comparative Study

Unsaturated Side Chain beta-11-hydroxyhexahydrocannabinol Analogs

J Busch-Petersen et al. J Med Chem.


The cannabinoid side chain is a key pharmacophore in the interaction of cannabinoids with their receptors (CB1 and CB2). To study the stereochemical requirements of the side chain, we synthesized a series of cannabinoids in which rotation around the C1'-C2' bond is blocked. The key steps in the synthesis were the cuprate addition of a substituted resorcinol to (+)-apoverbenone, the TMSOTf-mediated formation of the dihydropyran ring, and the stereospecific introduction of the beta-11-hydroxymethyl group. All the analogs tested showed nanomolar affinity for the receptors, the cis-hept-1-ene side chain having the highest affinity for CB1 (Ki = 0.89 nM) and showing the widest separation between CB1 and CB2 affinities. The parent n-heptyl-beta-11-hydroxyhexahydrocannabinol was the least potent binding to CB1 (Ki = 8.9 nM) and had the lowest selectivity between CB1 and CB2.

Similar articles

See all similar articles

Cited by 9 PubMed Central articles

See all "Cited by" articles

Publication types


LinkOut - more resources