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-C 5 ) and cannabidiol (CBD-C 5 ) were prepared from olivetol via regioselective condensation. Further treatments of CBD led to Δ 9 -tetrahydrocannabinol (THC-C 5 ), Δ 8 - iso -tetrahydrocannabinol ( iso -THC-C 5 ), and cannabinol (CBN-C 5 ). Alternatively, a [3 + 3] annulation between olivetol and citral yielded the minor cannabinoid cannabichromene (CBC-C 5 ), which was converted into two very rare polycycles, cannabicyclol (CBL-C 5 ) and cannabicitran (CBT-C 5 ), 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.