AUTHOR=Gurgone Lucía , La-Venia Agustina , Caprioglio Diego , Riveira Martín J. 

TITLE=Synthetic approaches to cis-THC, a promising scaffold in medicinal chemistry

JOURNAL=Frontiers in Natural Products

VOLUME=2

YEAR=2023

URL=https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2023.1225627

DOI=10.3389/fntpr.2023.1225627

ISSN=2813-2602

ABSTRACT=<p>The chemistry of phytocannabinoids has witnessed renewed interest these last decades as a consequence of reduced restrictions, research on the endocannabinoid system and the development of approved therapeutic treatments based on cannabinoids. The medicinal cannabinoid market constitutes a prolific scenario in current medicine. Most studies, however, have focused on only two major components of <italic>Cannabis sativa</italic> L., namely, cannabidiol (CBD, <bold>2</bold>) and (−)-Δ<sup>9</sup>-<italic>trans</italic>-tetrahydrocannabinol (Δ<sup>9</sup>-<italic>trans</italic>-THC, <bold>6a</bold>), the latter being the main psychoactive compound of this plant. The <italic>cis</italic>-diastereoisomer of Δ<sup>9</sup>-<italic>trans</italic>-THC, Δ<sup>9</sup>-<italic>cis</italic>-THC, although also present in the same plant, has been less investigated in terms of biological, medicinal and synthetic perspectives. Interestingly, the <italic>cis</italic>-fused tetrahydrobenzo [<italic>c</italic>]chromene motif present in Δ<sup>9</sup>-<italic>cis</italic>-THC is embedded in many other natural products which also exhibit interesting biological activities such as anticancer, antifungal, and antiparasitic. This review discloses synthetic approaches that have been established towards the <italic>cis</italic>-fused tetrahydroisochromene system of Δ<sup>9</sup>-<italic>cis</italic>-THC.</p>