Tunable normal phase enantioselectivity of amino acid esters via mobile phase composition

In this work, the effect of ESA modifier was studied for the enantioseparation of six pairs of amino acid esters on a CHIRALPAK® IA column, an immobilized amylose-based CSP, with different combinations of standard solvents (hexane and ethanol) as well as “non-standard” solvents, such as methyl t-butyl ether, ethyl acetate, tetrahydrofuran, acetone, or 1,4-dioxane. ESA generally improved selectivity, and multiple instances of elution order reversal were observed. A Van Deemter plot study reveals that ESA exerts its effect by pulling the enantiomer deeper into the chiral cavity of the chiral polymer to increase the interactions between the analytes and the stationary phase, which is the main reason for the increased enantioselectivity.