Alice Maiocchi, Marco Fumagalli, Manuel Vismara, Asja Blanco, Stefano Piazza, Giulia Martinelli, Valerio Fasano, Mario Dell’Agli, Daniele Passarella
J. Nat. Prod. 2024, ASAP
Despite millennia of therapeutic plant use, deliberate exploitation of Cannabis’s diverse biomedical potential has only recently gained attention. Bioactivity studies focus mainly on cannabidiol (CBD) and tetrahydrocannabinol (THC) with limited information about the broader cannabinome’s “minor phytocannabinoids”. In this context, our research targeted the synthesis of minor cannabinoids containing a lateral chain with 3 or 4 carbon atoms, focusing on cannabigerol (CBG) and cannabichromene (CBC) analogues. Using known and innovative strategies, we achieved the synthesis of 11 C3 and C4 analogues, five of which were inhibitors of skin inflammation, with the CBG-C4 ester derivative emerging as the most potent compound.