ROLE OF HYDROXYL-GROUPS IN CHIRAL RECOGNITION OF CANNABINOIDS BY CARBAMATED AMYLOSE

The enantioselective retention of four pairs of enantiomeric cannabinoids that have hydroxyl groups was compared with that for the corresponding acetylated compounds, using amylose tris(3,5-dimethylphenylcarbamate) in the stationary phase. According to this study the hydroxyl groups were essential to the chiral discrimination by the amylose stationary phase, since blocking them by acetylation was detrimental to the enantioselective separation. Three of the four enantiomeric pairs had a relatively rigid tricyclic backbone, whereas the fourth, the cannabidiol, was a flexible compound. In contrast to the other three enantiomeric pairs, the resolution of the acetylated cannabidiol was not completely lost as a result of the acetylation, but it was decreased and the elution order was reversed. Conformational analysis of the acetylated and non-acetylated enantiomeric pairs was systematically performed, using molecular mechanics, in order to examine the effect of acetylation on the conformation of the molecules. The results indicated that acetylation did not change the conformations substantially and therefore the loss of resolution was attributed to the blockage of the hydroxyl groups. The molecular mechanics approach was validated by comparing the energy-minimized structure of cannabidiol with its X-ray crystallographic structure taken from the literature.