The evolving science of phytocannabinoids

Abstract

The cannabis plant has had a tumultuous past. Once revered for its medicinal properties, it then became a banned narcotic and now the perceived medical benefits of cannabis see it receiving renewed attention. The active ingredients in cannabis plant extracts — phytocannabinoids — are now being investigated, both as formulations and in isolation, for pharmaceutical applications. The most abundant phytocannabinoid is (−)-trans9-tetrahydrocannabinol, a compound readily extracted from Cannabis sativa. There are over 100 known phytocannabinoids, some of which are present in such low concentrations that chemical syntheses are necessary to advance their medicinal potential. In this Review, we examine phytocannabinoids in terms of their mode of action, biosynthesis, and various total syntheses and derivatizations. Finally, we describe the policy issues surrounding the possession, use and control of phytocannabinoids.

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Figure 1: History of phytocannabinoids.
Figure 2: X-ray crystal structures of CB1 complexes of exogenous ligands.
Figure 3: Biosynthetic pathways to phytocannabinoids.
Figure 4: Synthetic approaches to Δ9-tetrahydrocannabinol.
Figure 5: Preparation of CBN (13a) by dimethylation of biaryl lactone derivatives.
Figure 6: Synthetic methods for phytocannabinoids from the CBG (8), CBC (9) and CBL (10) families, as well as metabolites of related compounds.

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Acknowledgements

The National Health and Medical Research Council (NHMRC)-EU collaborative grant and The Lambert Initiative for Cannabinoid Research, The University of Sydney, are acknowledged for funding.

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Reekie, T., Scott, M. & Kassiou, M. The evolving science of phytocannabinoids. Nat Rev Chem 2, 0101 (2018). https://doi.org/10.1038/s41570-017-0101

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