Enantioseparation of phenylsuccinic acid enantiomers based on aqueous two-phase system with ethanol/ammonium sulfate: phase diagrams optimization and partitioning experiments

Abstract

In the study herein we focused on enantioseparation of phenylsuccinic acid (PSA) enantiomers using an aqueous two-phase system (ATPS) composed of ethanol and ammonium sulfate. Based on phase-forming points and salting-out points, a modified phase diagram of ethanol/ammonium sulfate system with three distinct phase areas, including homogeneous area, ATPS area and salting-out area, has been constructed experimentally. The ATPS optimization and evaluation of chiral separation efficiency for PSA enantiomers have been investigated thoroughly. A hydrophilic chiral selector, hydroxypropyl-β-cyclodextrin (HP-β-CD), which has good chiral recognition ability for R-PSA, was added into bottom phase. The chiral separation efficiencies, namely distribution coefficients and separation factor, were affected by various process variables, including phase compositions of ATPS, concentrations of HP-β-CD and PSA enantiomers, pH value and operational temperature. Under the optimum conditions, separation factor could reach 1.42 after just one step extraction. This environmentally benign chiral separation technique opens up new possibilities for preparative separation of other racemic compounds at a large-scale.