L-酒石酸二乙酯萃取拆分氧氟沙星对映体的研究

Enantiseparation of Ofloxacin Enantimers via Diethyl L-Tartrate Extraction

左旋氧氟沙星是临床上常用的抗菌消炎药物,对于格兰阴性菌引起的各类炎症都有较好的治疗效果,其制备的一种方法是通过氧氟沙星消旋体进行手性拆分。手性拆分过程中氧氟沙星溶解度低、选择性系数小是目前急需解决的问题。研究使用乙酸增加了氧氟沙星在水相的溶解度,并利用L-酒石酸二乙酯对较高浓度的氧氟沙星进行了手性拆分。研究了萃取温度、L-酒石酸二乙酯浓度、氧氟沙星消旋体浓度以及乙酸浓度对于拆分过程的影响。结果表明,乙酸的加入能显著增大氧氟沙星在水相中的溶解度,在L-酒石酸二乙酯的浓度0.2 mol?L^(-1),氧氟沙星浓度12000 ppm,萃取温度25℃,乙酸浓度0.1 mol?L^(-1)时,氧氟沙星对映体的手性拆分系数达到1.39。这对左旋氧氟沙星的制备有较重要的参考价值。

Levofloxacin is a widely used antibacterial drug which has extraordinary therapeutic effects for alltypes of inflammation caused by Gran-negative bacteria.Currently,levofloxacin is usually produced viaenantioseparation,and low solubility and selectivity of ofloxacin enantiomers are the main problems needed tobe solved.This work used acetic acid as a cosolvent to increase ofloxacin solubility in water,and diethylL-tartrate was used to enantiseparate ofloxacin enantiomers.Effects of extraction temperature,and diethylL-tartrate,acetic acid and ofloxacin enantiomer concentration on enantiseparation were studied.The resultsshow that the addition of acetic acid can significantly increase ofloxacin solubility in aqueous phase.When theconcentrations of diethyl L-tartaric,ofloxacin and acetic acid one are0.2mol.L-1,12000ppm and0.1mol.L-1,respectively,the ofloxacin enantiomer chiral separation coefficient is1.39at25℃.The results obtained in thisstudy are helpful for large-scale levofloxacin manufacture.