Degree and distribution of substitution of hydroxypropyl-β-cyclodextrin in enantioselective liquid-liquid extraction and countercurrent chromatographic enantioseparation

Abstract

Nine types of hydroxypropyl-β-cyclodextrin (HP-β-CD) with different degrees and distributions of substitution were synthesised, and nine racemates were selected to investigate the effect of different degrees and distributions of substitution of HP-β-CD on the enantioseparation factor. 1H NMR and GC/MS were used to characterise the synthesised HP-β-CD. The degree and distribution of substitution had a significant influence on enantioselective liquid-liquid extraction and enantioseparation by countercurrent chromatography. For most of the tested racemates, increasing both the degree of substitution and distribution of substitution at the C-2 position for HP-β-CD would lead to an increasing enantioseparation factor; the optimal enantioseparation factor of 2-phenylbutyric acid, tropic acid, 2,3-diphenylpropionic acid, 2-(4-hydroxylphenyl) propanoic acid, and naproxen was increased to 1.77, 1.53, 1.67, 1.61, and 1.75, respectively. The enantioseparation of racemic naproxen, 2-(4-hydroxylphenyl) propanoic acid, and 2,3-diphenylpropionic acid by countercurrent chromatography was optimised using HP-β-CD with a degree of substitution of 16.5, and peak resolution was significantly improved to 1.03, 1.35, and 1.01, respectively.