Enantioseparation Of Aromatic α-hydroxyl Carboxylic Acids By Chiral Ligand Exchange Countercurrent Chromatography

This work concentrates on the enantioseparation of racemic aromatic α-hydroxyl acids,including ten kinds of mandelic acid derivatives and 3-phenyllactic acid by chiral ligand exchange high-speed countercurrent chromatography(HSCCC)and an equilibrium model of enantioseparation mandelic acid was developed.For the successful enantioseparation of racemic aromatic α-hydroxyl acids in HSCCC,the enantioselective liquid-liquid extraction was performed to determine the distribution ratio of enantiomers and to investigate the effects of influence factors on distribution ratio and enantioseparation factor.Seven of the racemates were successfully enantioseparated by analytical apparatus with an optimized solvent system.The two-phase solvent system was composed of n-butanol-water or hexane-n-butanol-water,to which N-n-dodecyl-L-proline or N-n-dodecyl-L-hydroxyproline was added in the organic phase as chiral ligand and cupric acetate was added in the aqueous phase as transition metal ion.Successful enantioseparation of 72 mg of mandelic acid,76 mg of 2-chloromandelic acid,74 mg of 4-methoxymandelic acid were achieved individually with high resolution.The HPLC purity of all enantiomers was over 96% with the recovery in the range of 82-90% from the collected fractions.Enantioseparation of 2-chloromandelic acid,4-methoxymandelic acid,4-hydroxymandelic acid,4-hydroxy-3-methoxymandelic acid and 3-chloromandelic acid by chiral ligand exchange mobile phase liquid chromatography were investigated.The relationship between retention factor and concentration of the binary complex was proven to be in conformity with chromatographic retention mechanism in which chiral discrimination occurred both in mobile and stationary phase.Meanwhile,an equilibrium model based on partition equilibria,dissociation equilibria and ligand exchange chemical equilibria and mass conservation principle was established in enantioseparation of mandelic acid by chiral ligand exchange HSCCC.The model was verified experimentally with excellent prediction of enantioseparation performance.And the all average relative deviations were less than 12%,which indicated that the established model could provide a single computational approach to process optimization in chiral ligand exchange countercurrent chromatography.