Enantioselective liquid-solid extraction for screening of structurally related chiral stationary phases

An enantioselective liquid-solid batch extraction method is described for t he screening of novel chiral stationary phases (CSPs) during optimization s tudies of chiral selectors derived form a common lead structure. Extraction enantioselectivity (a) values can be calculated from the enantiomeric exce ss ee-values of the selectand, which are measured in the liquid phase by en antioselective :HPLC. Extraction alpha-values have been correlated with chr omatographic alpha-values. The influence was studied of several experimenta l parameters of the assay (pH(a), buffer concentration, temperature, select or/selectand and phase ratio) on the enantiomeric excess (ee) values of the selectands and the enantioselectivity of the CSPs, respectively. The deriv ed statistically significant model has then been implemented to predict chr omatographic alpha-values of novel CSPs. For example, an ee of 89.3% for DN B-Leu as selectand could be achieved in batch extraction for a novel synthe sized but mechanistically similarly-acting CSP derived form quinine. This c orresponds to a calculated extraction alpha-value of 17.7. Based on this al pha(extraction) a chromatographic alpha-value of 28.8 was predicted by the linear correlation model; the experimental HPLC alpha-value of 31.7 was in good agreement and demonstrated the validity of the proposed screening meth od. The method is particularly helpful in SO optimization studies.