Stereoselective Synthesis of Nonpsychotic Natural Cannabidiol and Its Unnatural/Terpenyl/Tail-Modified Analogues

• DOI: 10.1021/acs.joc.1c02571
• Publication Date: 2022-03-15T11:51:54Z
• Authors: Radhika Anand; Pankaj Singh Cham; Veeranjaneyulu Ga...; Sumit Sharma; Mukesh Kumar; Rohit Singh; Ram A. Vishwakarma; Parvinder Pal Singh
• Keywords: Cannabidiol; 01 natural sciences; 0104 chemical sciences; 3. Good health

Here, we report a three-step concise and stereoselective synthesis route to one of the most important phytocannabinoids, namely, (-)-cannabidiol (-CBD), from inexpensive and readily available starting material R-(+)-limonene. The synthesis involved the diastereoselective bifunctionalization of limonene, followed by effective elimination leading to the generation of key chiral p-mentha-2,8-dien-1-ol. The chiral p-mentha-2,8-dien-1-ol on coupling with olivetol under silver catalysis provided regiospecific (-)-CBD, contrary to reported ones which gave a mixture. The newly developed approach was further extended to its structural analogues cannabidiorcin and other tail/terpenyl-modified analogues. Moreover, its opposite isomer (+)-cannabidiol was also successfully synthesized from S-(-)-limonene.