O-Methyl Phytocannabinoids: Semi-synthesis, Analysis in Cannabis Flowerheads, and Biological Activity

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.