MOLECULAR PHARMAcoLoGY, 35:495-503 The Conformational Analysis of - and z9’11- Tetrahydrocannabinols in Solution using High Resolution Nuclear Magnetic Resonance Spectroscopy

The conformation for each of two cannabinoids, 9-tetrahydro-cannabinol (THC), the principal active constituent of marihuana, and \911-THC, a biologically inactive structural isomer of THC, is analyzed by interpreting 1H-1H and 13C-1H coupling constants and nuclear Overhauser effects determined using one-and two-dimensional 1H and 13C NMR techniques. The interpre-tation of both Vicinal and long range coupling constants was necessary to deduce the conformations of these tricyclic mole-cules with certainty, with nuclear Overhauser eftect enhance-ments used, when appropriate, to confirm the results. These findings provide insights into the structure-activity requirements for the cannabinoids. The pharmacological properties and structure-activity rela-tionships of cannabinoids are well documented in the literature (1-4). However, very little is understood regarding the relation