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.

Identification and Characterization of Cannabichromene’s Major Metabolite Following Incubation with Human Liver Microsomes

“…After structural identification, the next step was to determine if the metabolite binds to CB 1 and CB 2 receptors and to compare its binding to that of CBC. Simulations were performed comparing the binding of Δ 9 -THC, CBC, 2′-hydroxycannabicitran, and CBT-C to both CB 1 R and CB 2 R. Importantly, since natural and synthetic CBC exists as a racemic mixture of enantiomers [ 23 , 37 , 48 , 49 , 50 ], we considered the stereospecificity of the ligands to the orthosteric site and modeled (−)-Δ 9 -THC, (+)-CBC, (−)-CBC, (R)-2′-hydroxy-(+)-cannabicitran, (S)-2′-hydroxy-(−)-cannabicitran, (+)-CBT-C, and (−)-CBT-C (structures are available in the Supplementary Materials Section S4.1 ). We utilized both Standard-Precision (SP) and Extra-Precision (XP) glide models to rank all ligands according to their docking scores.…”

Modern Mineral Oil Hydrocarbon Analysis

“…Evidence showing that both reversed-phase and normal-phase chiral HPLC can be used for enantio-purification based on polysaccharide stationary phases is reported in some recently published studies (49)(50)(51).…”

Preparation and Enantiomeric Separation of l-Pro-l-Phe-l-Val-l-Leu Peptide Stationary Phases

“…Therefore, the studies upon CSPs and chiral recognition mechanism were always attractive in past decades [10,11,12]. Till now, there have been numerous studies on natural CSPs including polysaccharides [13,14], macrocyclic glycopeptides [15,16], proteins [17], cyclodextrins [18], and arti cial CSPs such as crown ethers [19,20], chiral porous materials [21,22] and Pirkle-type materials [23]. Hence, the development of more versatile CSPs with high enantioselectivity and low cost continues to be a research focus.…”