Atropisomeric separation of a 2-aryl-imino-N-(2-aryl)-thiazoline compound by reversed phase HPLC using hydroxypropyl-g-cyclodextrin

Abstract

The fact that atropisomers of a biologically active compound exhibit different activities has attracted worldwide attention. The pharmacological activity of a chiral molecule can vary from one atropisomer to the other. Therefore, it is essential to separate the different atropisomers in order to be able to carry out the various biological tests; an inevitable step in the drug development process. In this study, the separation of racemic-N-[(2Z)-4-methyl-3-(2-methylphenyl)-1,3-thiazol-2(3H)-ylidene]-N-(2-chlorophenyl)amine to collect its atropisomers has been achieved by HPLC using hydroxypropyl-?-cyclodextrin (HP???CD) (to obtain chiral molecules) and hexane-propane-2-ol as a mobile phase. The optimum conditions of resolution were established by systematically studying the effect of the mobile phase, the CD concentrations and the time of incubation of the CD-substrate.