RT Journal Article
T1 The Oxidation of Phytocannabinoids to Cannabinoquinoids.
A1 Caprioglio, Diego
A1 Mattoteia, Daiana
A1 Pollastro, Federica
A1 Negri, Roberto
A1 Lopatriello, Annalisa
A1 Chianese, Giuseppina
A1 Minassi, Alberto
A1 Collado, Juan A
A1 Munoz, Eduardo
A1 Taglialatela-Scafati, Orazio
A1 Appendino, Giovanni
AB Spurred by a growing interest in cannabidiolquinone (CBDQ, HU-313, 2) as a degradation marker and alledged hepatotoxic metabolite of cannabidiol (CBD, 1), we performed a systematic study on the oxidation of CBD (1) to CBDQ (2) under a variety of experimental conditions (base-catalyzed aerobic oxidation, oxidation with metals, oxidation with hypervalent iodine reagents). The best results in terms of reproducibility and scalability were obtained with λ5-periodinanes (Dess-Martin periodinane, 1-hydroxy-1λ5,2-benziodoxole-1,3-dione (IBX), and SIBX, a stabilized, nonexplosive version of IBX). With these reagents, the oxidative dimerization that plagues the reaction under basic aerobic conditions was completely suppressed. A different reaction course was observed with the copper(II) chloride-hydroxylamine complex (Takehira reagent), which afforded a mixture of the hydroxyiminodienone 11 and the halogenated resorcinol 12. The λ5-periodinane oxidation was general for phytocannabinoids, turning cannabigerol (CBG, 18), cannabichromene (CBC, 10), and cannabinol (CBN, 19) into their corresponding hydroxyquinones (20, 21, and 22, respectively). All cannabinoquinoids modulated to a various extent peroxisome proliferator-activated receptor gamma (PPAR-γ) activity, outperforming their parent resorcinols in terms of potency, but the iminoquinone 11, the quinone dimers 3 and 23, and the haloresorcinol 12 were inactive, suggesting a specific role for the monomeric hydroxyquinone moiety in the interaction with PPAR-γ.
PB American Chemical Society
YR 2020
FD 2020-04-21
LK http://hdl.handle.net/10668/15401
UL http://hdl.handle.net/10668/15401
LA en
NO Caprioglio D, Mattoteia D, Pollastro F, Negri R, Lopatriello A, Chianese G, et al.  The Oxidation of Phytocannabinoids to Cannabinoquinoids. J Nat Prod. 2020 May 22;83(5):1711-1715
NO We thank MIUR for financial support to the groups in Novara and Naples(PRIN2017, Project No. 2017WN73PL, Bioactivity-directed exploration of the phytocannabinoid chemical space).
DS RISalud
RD Apr 12, 2025