Novel Synthesis of C-Methylated Phytocannabinoids Bearing Anti-inflammatory Properties

There is growing interest in non-psychoactive phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), and cannabichromene, as potential leads for novel therapeutic agents. In this study, we report on the development of new derivatives in which we methylated either position 4 of olivetol or the phenolic positions of olivetol, or both. We introduce a refinement on previously reported chemical procedures for phytocannabinoid derivatization as well as the biological evaluation of all derivatives in anti-inflammatory in vivo models. Compounds such as the CBD derivative, 2 and the CBG derivative, 11, significantly reduced cytokine levels when compared to their parent compounds. Moreover, both of these derivatives proved to be as potent as dexamethasone for the inhibition of IL-1 beta. We believe that these new derivatives, as described herein, can be further developed as novel drug candidates for inflammatory conditions.

Automated summary

There is growing interest in non-psychoactive phytocannabinoids, such as CBD, CBG, and CBC, as potential therapeutic agents. This study developed new derivatives by methylating positions of olivetol and evaluated their anti-inflammatory effects. The CBD derivative, 2, and the CBG derivative, 11, showed significant reduction in cytokine levels and were as potent as dexamethasone in inhibiting IL-1 beta. These new derivatives have potential as novel drug candidates for inflammatory conditions.