Synthetic Strategies for Rare Cannabinoids Derived from Cannabis sativa

Efficient syntheses of eight key cannabinoids were established and optimized. Predominant cannabinoids such as cannabigerol (CBG-C₅) and cannabidiol (CBD-C₅) were prepared from olivetol via regioselective condensation. Further treatments of CBD led to Δ⁹-tetrahydrocannabinol (THC-C₅), Δ⁸-iso-tetrahydrocannabinol (iso-THC-C₅), and cannabinol (CBN-C₅). Alternatively, a [3 + 3] annulation between olivetol and citral yielded the minor cannabinoid cannabichromene (CBC-C₅), which was converted into two very rare polycycles, cannabicyclol (CBL-C₅) and cannabicitran (CBT-C₅), in a one-pot reaction. Finally, all eight syntheses were extended by utilizing resorcinol and two phenolic analogues, achieving a cannabinoid group with more than 30 compounds through a facile synthesis strategy.