Enantioseparation Of Aromatic Carboxylic Acids And Its(-)-Menthol Esters By Countercurrent Chromatography

This paper concentrates on enantioseparation of racemic aromatic carboxylic acids by high speed countercurrent chromatography with substituted ?-cyclodextrin as chiral selector.First,four 2-(substituted phenyl)propanoic acids were separated by high countercurrent chromatography with hydroxypropyl-?-cyclodextrin as the chiral mobile phase additive and the influence of substituent on the benzene ring in enantiorecognition between chiral selector and enantiomer of each racemate were considered.Then,(-)-menthol was used as chiral derivatization reagent for esterification of racemic aromatic acids.The separated of epimeric aromatic acid(-)-menthol eaters by high countercurrent chromatography for their different space structure.Totally ten of racemic 2-(substituted phenyl)propanoic acids were investigated,including 2-(4-methylphenyl)propanoic acid,2-(4-hydroxyphenyl)propanoic acid,2-(4-chlorophenyl)propanoic acid,2-(4-nitrophenyl)propanoic acid,naproxen,ibuprofen,ketoprofen,suprofen,mandelic acid,3-chloromandelic acid,4-bromomandelic acid and 4-hydroxyl-3-methoxymandelic acid.1.The enantioseparation of 2-(substituted phenyl)propanoic acids was established by high performance liquid chromatography with hydroxypropyl-?-cyclodextrin as the chiral mobile phase additive and a C18 reversed-phase column was used as the stationary phase.Influence factors for peak resolution were investigated,and the influence of type of substituent on the benzene ring in enantiorecognition between chiral selector and enantiomer of each racemate were considered.The results showed that the stoichiometries for all the inclusion complex of hydroxypropyl-?-cyclodextrin and enantiomers were 1:1.By calculating the ratio of the binding constants and comparing different substituent group of 2-(substituted aryl)propanoic acids,it was found that the electron donating group is more advantageous to enantiorecognition with enantiomer by hydroxypropyl-?-cyclodextrin.Two 2-(substituted phenyl)propanoic acids was successfully separated by high countercurrent chromatography with hydroxypropyl-?-cyclodextrin as the chiral mobile phase additive.2.(-)-Menthol was used as chiral derivatization reagent for esterification of racemic aromatic acids.The separation of ten epimeric aromatic acid(-)-menthol eaters by high performance liquid chromatography was established and a C18 reversed-phase column as the stationary phase.A biphasic solvent system composed of n-hexane :20-70 % methanol containing 50 mmol L-1 of hydroxypropyl-?-cyclodextrin(1:1,v/v)were selected,which provided high separation factors for five of the epimeric esters and successful separations by countercurrent chromatography were achieved.Complete separation of five pairs of epimeric ester was obtained with the purity being over 98 %for each peak fractions,as determined by HPLC.Recovery of each analyte from the eluted fractions reached around 80-88 %.