A Catalytic, Oxidative Synthesis of Olivetol, Methyl Olivetolate and Orthogonally Protected Methyl Ether Derivatives: D. Hurem, B. J. Macphail, R. Carlini, J. Lewis, J. McNulty
SynOpen 2021, 5, 86–90, DOI: 10.1055/a-1440-9732
Tetrahydrocannabinol (THC) and cannabidiol (CBD) have been identified among nearly 600 natural products that have been profiled in cannabis extracts and have attracted enormous attention owing to their pharmacological properties. Among the hundreds of less studied cannabinoids, olivetolic acid and olivetol are of particular interest, as these compounds are also key intermediates in the biosynthesis of other phytocannabinoids. The group of Professor James McNulty from McMaster University (Hamilton, Ontario, Canada), has recently reported a new entry to olivetol, methyl olivetolate and several orthogonally protected methyl ether derivatives.
Professor McNulty said: “Access to cannabinoids bearing side chains alternative to the natural five-carbon derivatives is actively sought given their neurological effects manifest via modulating cannabinoid receptors. We report a catalytic oxidative approach to aromatization leading to the synthesis olivetol and olivetolate ester derivatives as well as orthogonally protected methyl ethers. The general synthesis opens various avenues for terpenylation reactions and access to structurally varied cannabinoids that will inform these biological investigations.”