Stereoselective Synthesis of Cannabidiol and its Unnatural Enantiomer to Evaluate Anxiolytic-Like Properties and Memory Interactions.

Abstract

(-)-Cannabidiol (CBD) is a nonpsychotropic phytocannabinoid found in Cannabis strains with well-established pharmacological applications. Conversely, (+)-cannabidiol (ent-CBD), the non-natural enantiomer of CBD, has been involved in a limited number of pharmacological studies. Therefore, CBD and ent-CBD are synthesized using (R)-(-)- and (S)-(+)-carvone as starting materials, respectively, via a highly diastereoselective 10-camphorsulfonic acid (CSA) catalyzed Friedel-Crafts reaction as the key step. Pharmacological studies are conducted using the plus-maze discriminative avoidance task (PM-DAT) to evaluate the interaction between memory and anxiety-like behavior as well as spontaneous motor activity in both young adult and aged male mice. The results show that ent-CBD at a dose of 20 mg kg^-1 has an anxiolytic-like effect in aged male mice. In addition, ent-CBD did not impair discriminative avoidance memory formation at all doses evaluated.