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

J Org Chem. 2022 Apr 1;87(7):4489-4498. doi: 10.1021/acs.joc.1c02571. Epub 2022 Mar 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cannabidiol*

Substances

  • Cannabidiol