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-1β.
We believe that these new derivatives, as described herein, can be
further developed as novel drug candidates for inflammatory conditions.