Caprioglio, DiegoMattoteia, DaianaPollastro, FedericaNegri, RobertoLopatriello, AnnalisaChianese, GiuseppinaMinassi, AlbertoCollado, Juan AMunoz, EduardoTaglialatela-Scafati, OrazioAppendino, Giovanni2023-02-082023-02-082020-04-21Caprioglio 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):1711-1715http://hdl.handle.net/10668/15401Spurred 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.enCannabidiolCannabinoidsOxidation-ReductionPPAR gammaQuinonesReproducibility of ResultsResorcinolsresearch article32315173open accessCannabinoidesOxidación-reducciónPPAR gammaQuinonasReproducibilidad de los resultadosResorcinoles10.1021/acs.jnatprod.9b012841520-6025PMC7997633https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.9b01284https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997633/pdf