Preparation of a bis-triazolyl bridged β-cyclodextrin stationary phase and its application for enantioseparation of chiral compounds by HPLC

Abstract

A novel bis-triazolyl bridged β-cyclodextrin was first synthesized by the Click reaction between azido-β-cyclodextrin and 1,6-heptadiyne. Then it was bonded onto silica gel to obtain a bis-triazolyl bridged β-cyclodextrin-based chiral stationary phase (BCDP). After structure characterization, the HPLC performance of BCDP was systematically evaluated by using different types of compounds as probes. The results showed that BCDP could well separate 18 kinds of achiral aromatic compounds (homologues, positional isomers, etc.) and 35 kinds of chiral drugs or pesticides, such as triazoles (Rs = 1.33–3.15), flavanones (Rs = 1.49–2.62), dansyl amino acids (Rs = 0.96–1.99), and β-blocker drugs (Rs = 0.68–2.78). BCDP could separate a wider range of compounds (53 kinds); especially, some chiral substance pairs that were difficult to be resolved on the ordinary cyclodextrin CSPs, including triazoles containing two chiral carbons (triadimenol, bitertanol, metconazole, and triticonazole), strongly ionized amino acids (acidic Asp, alkalic Arg, and polar Thr) and β-blockers with bulky groups (carvedilol, propranolol, and pindolol). Obviously, the unique synergistic inclusion effect of bridged cyclodextrin with double cavities and the bis-triazole bridging group could provide multiple action sites, such as hydrogen bonding, π-π stacking and acid–base action sites, thus improving its chiral chromatographic performance.