Investigation of the structure–selectivity relationships and van’t Hoff analysis of chromatographic stereoisomer separations of unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids on Cinchona alkaloid-based chiral stationary phases

• Stereoisomer separation of isoxazoline-fused 2-aminocyclopentanecarboxylic acids on Cinchona-alkaloid based CSPs.
• Mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes.
• Thermodynamic parameters were calculated at constant mobile phase compositions in the temperature range 5–50 °C.
• Both enthalpically- and entropically-controlled chiral separations were observed.

The enantiomers of four unusual, rather rigid isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the structures of the analytes and temperature on the separations were investigated. Experiments were performed at constant mobile phase composition in the temperature range 10–50 °C to study the effects of temperature, and thermodynamic parameters were calculated from plots of ln α versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomer separations were in most cases predominantly enthalpy-driven, but entropically-driven separations were also observed. The sequence of elution of the enantiomers was determined in all cases.