“One-pot” click access to triazole bridged cyclodextrin chiral phases for differentiation of clopidogrel enantiomers

Abstract

The current work demonstrates a “one-pot” click synthetic procedure for the preparation of triazole bridged cyclodextrin (CD) chiral stationary phases (CSPs) and their application for efficient chiral differentiation of clopidogrel enantiomers under reversed-phase high performance liquid chromatography (HPLC). It was found that native-CD-CSPs and methylated-CD-CSPs showed good enantioselectivity towards clopidogrel enantiomers with acetonitrile (ACN)/water and methanol (MeOH)/water as mobile phases, respectively, while the more versatile phenylcarbamoylated-CD-CSP cannot resolve the enantiomers due to the steric hindrance of bulky phenylcarbamate moieties. Solvent selection plays an important role in CSP chiral recognition ability towards clopidogrel enantiomers. 6-Hydroxyl moieties on CD rims were found to participate in the chiral recognition process. The optimal chiral resolution (R_s) was improved to 1.95 by transferring the separation from 5 μm native-CD-CSPs to 3 μm native-CD-CSPs with ACN/buffer as the mobile phase.