Article first published online: 11 FEB 2010
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Organic Chemistry
Volume 2010, Issue 11, pages 2067–2072, April 2010
- Aldol reactions;
- Biomimetic synthesis;
- Cannabinoid receptors;
An investigation of the polar fractions from a nonpsychotropic variety of hemp (Cannabis sativa L.) afforded cannabimovone (6), a polar cannabinoid with a rearranged 2(34) abeo-terpenoid skeleton, biogenetically originating from the intramolecular aldolization of a 2′,3′-seco-menthanyl precursor. The structure of cannabimovone was elucidated by spectroscopic analysis, whereas attempts to mimic its biogenetic derivation from cannabidiol (2) gave only anhydrocannabimovone (12), the intramolecular oxy-Michael adduct of the crotonized version (11b) of the elusive natural products. Biological evaluation of cannabimovone (6) against metabotropic (CB1, CB2) and ionotropic (TRPs) cannabinoid receptors showed a significant activity only for ionotropic receptors, especially TRPV1, whereas anhydrocannabimovone (12) exhibited strong activity at both ionotropic and metabotropic cannabinoid receptors. Overall, the biological profile of anhydrocannabimovone (12) was somewhat similar to that of THC (4), suggesting a remarkable tolerance to constitutional and configurational changes.