Synthesis and application of mono-2 A-azido-2 A-deoxyperphenylcarbamoylated β-cyclodextrin and mono-2 A-azido-2 A-deoxyperacetylated β-cyclodextrin as chiral stationary phases for high-performance liquid chromatography

Abstract

Two novel chiral stationary phases (CSPs) were prepared based upon the regioselective immobilizations of β-cyclodextrin (β-CD) at its C2 position to the silica support. The mono-2 A -azido-2 A -deoxyperphenylcarbamoylated β-cyclodextrin and mono-2 A -azido-2 A -deoxyperacetylated β-cyclodextrin were synthesized by selective tosylation and azidolysis followed by perfunctionalisation. The derivatised cyclodextrins were then immobilized onto the aminised silica gel via the Staudinger reaction to provide new chiral stationary phases. Their application to high-performance liquid chromatography (HPLC) enantioseparation of racemic compounds was demonstrated using β-adrenergic blockers, flavonone compounds, benzodiazepinones, antihistamines and weakly protolytic compounds, of which good separations were achieved for some racemic compounds, for instance, bendroflumethiazide ( R s 6.26), oxazepam ( R s 5.99), temazepam ( R s 2.85) and althiazide ( R s 1.13) when compared with the corresponding CSPs where the β-CD molecule was regioselectively immobilized at the C6 position. The enantiodiscriminatory properties of these CSPs were found to be affected by the orientation of the CD cavity under reversed-phase conditions, and also by the derivitising groups of the CD. The HPLC results inferred that the mono-6 A -azido-6 A -deoxyperphenylcarbamoylated CD CSP (CD bonded at C6 position to silica) exhibited slightly better chiral recognition ability than mono-2 A -azido-2 A -deoxyperphenylcarbamoylated CD CSP under the normal-phase and reversed-phase modes on the separation of 31 different racemic compounds and drugs. On the contrary, higher chiral recognition abilities were observed on the mono-2 A -azido-2 A -deoxyperacetylated CD CSP compared to mono-6 A -azido-6 A -deoxyperacetylated CD CSP.