Novel enantioselective strong cation exchangers based on sulfodipeptide selectors: evaluation for enantiomer separation of chiral bases by nonaqueous capillary electrochromatography

Strong cation exchange (SCX)-type chiral stationary phases (CSPs) based on beta-amino sulfonic acid-terminated dipeptide derivatives as chiral selectors, immobilized on thiol-modified silica particles (3.5 microm), were synthesized and applied to enantiomer separations of chiral bases by nonaqueous capillary electrochromatography (CEC). The effect of structural variations of the sulfodipeptide selectors on the separation factors alpha was investigated. These studies included variation of the acid-terminal amino sulfonic acid residue, variation of the configurations, i.e., comparison of the diastereomeric (S,S)- and (R,S)-configurations of the sulfodipeptides, and finally comparison of sulfodipeptide selectors with corresponding beta-amino sulfonic acid analogs. In general, the capillary columns (100 microm ID) packed with the new SCX-type CSPs showed enantioselectivity for an elaborated set of chiral basic drugs in CEC acting by an enantioselective cation-exchange retention mechanism. N-[N-(4-Allyloxy-3,5-dichlorobenzoyl)-leucyl]-2-amino-3,3-dimethylbutane sulfonic acid, in particular with (R,S)-configuration, turned out to be a more effective SCX-type selector than a more rigid analog based on N-[N-(4-Allyloxy-3,5-dichlorobenzoyl)-leucyl]-2-pyrrolidinemethane sulfonic acid. Both of the former diastereomers were capable to baseline-resolve the enantiomers of ca. 40% of the tested basic chiral solutes including sympathomimetics and beta-blockers, while for the latter SCX-type CSPs only 10-20% of the selected solutes afforded resolutions > 1.5.