Cannabimovone, a Cannabinoid with a Rearranged Terpenoid Skeleton from Hemp

• Published in: European Journal of Organic Chemistry 2010-04, Vol.2010 (11), p.2067-2072
• Main Authors: Taglialatela-Scafati, Orazio, Pagani, Alberto, Scala, Fernando, De Petrocellis, Luciano, Di Marzo, Vincenzo, Grassi, Gianpaolo, Appendino, Giovanni
• Format: Article
• Language: English
• Subjects: Aldol­ reactions; Alicyclic compounds, terpenoids, prostaglandins, steroids; Biological and medical sciences; Biomimetic synthesis; Cannabinoid receptors; Chemistry; Drug addictions; Exact sciences and technology; General pharmacology; Hemp; Medical sciences; Organic chemistry; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytocannabinoids; Preparations and properties; Terpenoids; Toxicology
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200901464

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(3→4) 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. A nonpsychotropic variety of Cannabissativa L. afforded cannabimovone, a new type of cannabinoid characterized by a rearrranged terpenoid skeleton and a biological profile similar to that of cannabidiol. Attempts to prepare cannabimovone from cannabidiol gave only the intramolecular oxy‐Michael adduct of the crotonized natural product, a compound with a biological profile similar to that of THC.