Separation Of Pharmaceutical Enantiomers By Ligand Exchange Method Based On Chiral Ionic Liquids

In the past decades, With the research of the chiral substance and the importance of chiral molecules for use in production of pharmaceuticals and food products, considerable optical pure enantiomers were demanded. Chromatography especially the high performance liquid chromatography is the most active method. The chiral ligand exchange chromatography is a simple, effective and widely used mean of separation and accurate analytical methods for determination of enantiomeric purity. The chiral ligand exchange chromatography has several advantages that can be used in a normal column and the analysis cost is low. The chiral separation can be obtained by changing the selectors, the concentration of selectors and the composition of the mobile phase.Based on ligand exchange mechanism, ofloxacine (OFLX) enantiomers were successfully separated using [C4mim][Pro] as a chiral ligand coordinated with copper(Ⅱ), Separation conditions were optimized, where4mmol/L [C4mim][Pro] and3mmol/L Cu+were dissolved in methanol/water (20:80, v/v) with pH5.2at a flow rate of0.8mL/min. Based on the mechanism of ligand exchange, chiral ionic liquids was used to separate three substances as the following:Based on ligand exchange mechanism, phenylalanine enantiomers were successfully separated using [C4mim][Pro] as a chiral ligand coordinated with copper(Ⅱ), Under this conditions, the Phe enantiomers could be baseline separated effectively. And some thermodynamical parameters were evaluated. In the range of25±45℃, the values of△△H0and△△S0were both negative, and|△△H0>|T△△S0|, which showed that the chiral separation of Phe enantiomers was an enthalpy-controlled process. And the values of△H0of D-Phe were larger than those of L-Phe, indicating that L-Phe had stronger affinity to the stationary phase, which was consistent with the elution order of monomers.Based on the chiral ligand exchange mechanism, the liquid-liquid extraction method in the chiral ionic liquid/ethyl acetate system was used to separate the mandelic acid enantiomers. In this system, the role of chiral ionic liquid are solvent and extractant. The influcing factors such as the length of the alkyl chain of the chiral ionic liquids, chiral ionic liquids concentration, copper ion concentration, the concentration of racemic were studied. The optimal conditions were ethyl acetate as organic solvent, MA concentration of20mg/ml, ionic liquids [HMIM][L-Pro], the molar ratio of AAIL and copper ion of2:1, the extraction time of2.5min, extraction temperature of30℃with the enantioselectivity of1.53.