羧甲基-β-环糊精取代度对毛细管电泳手性拆分的影响

Effect of the degree of substitution of carboxymethyl-β-cyclodextrin on enantioseparation by capillary electrophoresis

目的:研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分影响。方法:以氯醋酸为羧甲基化试剂,通过调整物料比例合成了3种不同取代度的羧甲基-β-环糊精,并通过核磁共振直接对它们的平均取代度和取代位置进行表征;以萘哌地尔和吲哒帕胺为模型化合物,考察了不同取代度的羧甲基-β-环糊精对毛细管电泳手性拆分的影响。结果:随着羧甲基-β-环糊精取代度的增大,萘哌地尔分离随之改善;相反,吲哒帕胺对映体在较低取代度的羧甲基-β-环糊精条件下获得良好分离。结论:羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是至关重要的。

ABSTRACT：OBJECTIVE To investigate the effect of the degree of substitution （DS） of carboxymethyl-β-cyclodextrin （CM-β- CD） on chiral resolution by capillary electrophoresis （CE）. METHODS Firstly, three CM-β-CD with various average DS were synthesized by a facile single-step direct carboxymethylation of cyclodextrin using monochloroacetic acid in sodium hydroxide solution, and furthermore, the average DS and position of substitution of CM-β-CD were characterized directly by nuclear magnetic resonance （NMR）. Secondly, the effects of the DS of CM-β-CD on CE resolution of two racemates were evaluated. RESULTS The results showed that the DS had a different effects on the enantioseparation of two racemates because of different molecular structures. The resolution of naftopidil enantiomers increased with increasing DS, in contrast, the resolution of indapamide enantiomers decreased with the increase of DS. CONCLUSION The degree of substitution had a significant effect on the resolution of the optical isomers and the ionic strength of the running buffer. These different results clearly demonstrate that it is crucial to use well-characterized CD derivatives.