Chiral Separation of Cannabichromene, Cannabicyclol, and Their Acidic Analogs on Polysaccharide Chiral Stationary Phases

Abstract

Until recently, chirality has not been a major focus in the study of cannabinoids, as most cannabinoids of interest, such as cannabidiol and tetrahydrocannabinol, exist as a single isomer from natural sources. However, this is changing as more cannabinoids are identified, and compounds such as cannabichromene and cannabicyclol are emerging as potential investigatory candidates for varying indications. Because these molecules are chiral, the separation and study of the individual enantiomers’ biological and physiological effects should therefore be of interest. The purpose of this study was to identify analytical separation conditions and then adapt those conditions to preparative separation. This was accomplished with a column-screening approach on Daicel’s immobilized polysaccharide chiral stationary phases using non-traditional mobile phases, which included dichloromethane, ethyl acetate, and methyl tert-butyl ether under high-performance liquid chromatography conditions. CHIRALPAK® IK was found to separate all four compounds well with mobile phases containing hexane-dichloromethane (with or without an acidic additive). From these methods, the separation productivities were calculated to better visualize the separation scalability, which shows that the kilogram-scale separations of each are feasible.