Development of a high speed counter-current chromatography system with Cu(II)-chiral ionic liquid complexes and hydroxypropyl-β-cyclodextrin as dual chiral selectors for enantioseparation of naringenin

Cu(II) complexed amino acid ionic liquid, Cu(II)-[1-butyl-3-methylimidazolium][L-Pro] (Cu(11)-[BMIm][L-Pro]), was successfully adopted as chiral ligand to improve the enantioseparation efficiency in high speed counter-current chromatography (HSCCC). For the enantioseparation of intractable naringenin (NRG) racemic mixtures, Cu(II)-[BMIm][L-Pro] coupled with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was successfully applied as dual chiral selectors in HSCCC. The influence of important parameters, including the concentration of the chiral selectors, the pH value, and the temperature were investigated. Under optimal conditions, 4.5 mg of (+)-NRG and 4.1 mg of (-)-NRG were successfully separated from 10 mg NRG racemic mixtures with the purity of 98%. The chiral recognition mechanism of dual chiral selectors was illuminated by the UV-vis and NMR spectra, suggesting that the enantioseparation was upon the difference of the thermodynamic stability of the quaternary complexes of Cu(II), [BMIm][L-Pro], HP-beta-CD, and NRG. The results illustrated that the developed HSCCC system, based on the synergistic mechanism of Cu(II)-[BMIm][L-Pro] and HP-beta-CD, exhibited better performance on enantioseparation and had great application potential in preparative chiral separation of natural products. (C) 2016 Elsevier B.V. All rights reserved.