Enantiomeric cannabidiol derivatives: synthesis and binding to cannabinoid receptors

Abstract

(-)-Cannabidiol (CBD) is a major, non psychotropic constituent of cannabis. It has been shown to cause numerous physiological effects of therapeutic importance. We have reported that CBD derivatives in both enantiomeric series are of pharmaceutical interest. Here we describe the syntheses of the major CBD metabolites, (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series. The starting materials were the respective CBD enantiomers and their DMH homologs. The binding of these compounds to the CB(1) and CB(2) cannabinoid receptors are compared. Surprisingly, contrary to the compounds in the (-) series, which do not bind to the receptors, most of the derivatives in the (+) series bind to the CB(1) receptor in the low nanomole range. Some of these compounds also bind weakly to the CB(2) receptor.

Structure–Activity Relationships of Classical Cannabinoids

“…CBD does not bind to CB1 or CB2 receptors and even its DMH analogs [62] bind very weakly to both receptors. Thus (-)-CBD-DMH binds to the CB1 receptors with a K i above 10 mM and to the CB2 receptors with a K i of 1800 nM.…”

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation

“…The syntheses of the CBD derivatives, (−)-11-hydroxy-CBD, (−)-CBD-11-oic acid and their dimethylheptyl (DMH) analogs, as well as of the enantiomeric (+)-CBD series have been reported (Fig. 2) 8 . The affinities of these compounds for both the CB1 and CB2 receptors were measured with unexpected results.…”

Cannabidiol – Recent Advances

“…We have described the syntheses of the major CBD metabolites (À)-7-hydroxycannabidiol (5a) and the corresponding carboxylic acid 6a, their dimethylheptyl (DMH) homologues 5b and 6b, respectively, as well as the corresponding enantiomeric compounds in the (þ)-CBD series [22] [23]. The starting materials were the respective CBD enantiomers and their DMH homologues.…”