Subscribe to RSS
DOI: 10.1055/a-0883-5383
O-Methyl Phytocannabinoids: Semi-synthesis, Analysis in Cannabis Flowerheads, and Biological Activity[*]
Publication History
received 01 February 2019
revised 18 March 2019
accepted 20 March 2019
Publication Date:
01 April 2019 (online)
Abstract
A general protocol for the selective mono-O-methylation of resorcinyl phytocannabinoids was developed. The availability of semisynthetic monomethyl analogues of cannabigerol, cannabidiol, and cannabidivarin (1a–3a, respectively) made it possible to quantify these minor phytocannabinoids in about 40 different chemotypes of fiber hemp. No chemotype significantly accumulated mono-O-methyl cannabidiol (2b) or its lower homologue (3b), while at least three chemotypes containing consistent amounts (≥ 400 mg/kg) of O-methylcannabigerol (1b) were identified. O-Methylation of alkyl phytocannabinoids (1b–3b) does not significantly change the activity on peroxisome proliferator-activated receptors in contrast to what was reported for phenethyl analogues.
* Dedicated to Professor Dr. Cosimo Pizza 70th birthday in recognition of his outstanding contribution to natural product research.
-
References
- 1 Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G. Phytocannabinoids: a unified critical inventory. Nat Prod Rep 2016; 33: 1357-1392
- 2 Pollastro F, Taglialatela-Scafati O, Allarà O, Muñoz E, Di Marzo V, De Petrocellis L, Appendino G. Bioactive prenylogous cannabinoid from fiber hemp (Cannabis sativa). J Nat Prod 2011; 74: 2019-2022
- 3 Ahmed SA, Ross SA, Slade D, Radwan MM, Zulfiqar F, Matsumoto RR, Xu YT, Viard E, Speth RC, Karamyan VT, ElSohly MA. Cannabinoid ester constituents from high-potency Cannabis sativa . J Nat Prod 2008; 71: 536-542
- 4 Mechoulam R, Ben-Zvi Z, Gaoni Y. Hashish – XIII: On the nature of the beam test. Tetrahedron 1968; 24: 5615-5624
- 5 Yamauchi T, Shoyama Y, Matsuo Y, Nishioka K. Cannabigerol monomethyl ether, a new component of hemp. Chem Pharm Bull 1968; 16: 1164-1165
- 6 Shoyama Y, Kuboe K, Nishioka I, Yamaguchi T. Cannabidiol monomethyl ether. A new neutral cannabinoid. Chem Pharm Bull 1972; 20: 2072
- 7 Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009; 10: 515-527
- 8 Fuhr L, Rousseau M, Plauth A, Schroeder FC, Sauer S. Amorfrutins are Natural PPARγ Agonists with Potent Anti-inflammatory Properties. J Nat Prod 2015; 78: 1160-1164
- 9 Takeda S, Noriyuki U, Yamamoto I, Watanabe K. Cannabidiol-2′,6′-dimethylether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metab Dispos 2009; 37: 1733-1737
- 10 Presser A, Hufner A. Trimethylsilyldiazomethane – a mild and efficient reagent for the methylation of carboxylic acids and alcohols in natural products. Monatsh Chem 2004; 135: 1015-1022
- 11 Choi YH, Hazekamp A, Peltenberg-Looman AMG, Frederich M, Erkelens C, Lefeber AWM, Verpoorte R. NMR assignment of the major cannabinoids and cannabiflavonoids isolated from flowers of Cannabis sativa . Phytochem Anal 2004; 15: 345-354
- 12 Borrelli F, Pagano E, Romano B, Panzera S, Maiello F, Coppola D, De Petrocellis L, Buono L, Orlando P, Izzo AA. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis 2014; 35: 2787-2797