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

Nine types of hydroxypropyl- ,B-cyclodextrin (HP- ,B-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- ,B-CD on the enantioseparation factor. 1 H NMR and GC/MS were used to characterise the synthesised HP- ,B-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- ,B-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 2,3diphenylpropionic acid by countercurrent chromatography was optimised using HP- ,B-CD with a degree of substitution of 16.5, and peak resolution was significantly improved to 1.03, 1.35, and 1.01, respectively. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Nine types of hydroxypropyl- ,B-cyclodextrin with different degrees and distributions of substitution were synthesized to study their effect on enantioseparation factor. The results showed that the degree and distribution of substitution significantly influenced enantioselective liquid-liquid extraction and enantioseparation by countercurrent chromatography. Increasing the degree and distribution of substitution at the C-2 position for hydroxypropyl- ,B-cyclodextrin led to an increasing enantioseparation factor for most racemates tested. The optimal enantioseparation factor for 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.