Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds

Abstract

An extensive series of free amino acids and analogs were directly resolved into enantiomers (and stereoisomers where appropriate) by HPLC on zwitterionic chiral stationary phases (Chiralpak ZWIX(+) and Chiralpak ZWIX(-)). The interaction and chiral recognition mechanisms were based on the synergistic double ion-paring process between the analyte and the chiral selectors. The chiral separation and elution order were found to be predictable for primary α-amino acids with apolar aliphatic side chains. A systematic investigation was undertaken to gain an insight into the influence of the structural features on the enantiorecognition. The presence of polar and/or aromatic groups in the analyte structure is believed to tune the double ion-paring equilibrium by the involvement of the secondary interaction forces such as hydrogen bonding, Van der Waals forces and π-π stacking in concert with steric parameters. The ZWIX chiral columns were able to separate enantiomers and stereoisomers of various amphoteric compounds with no need for precolumn derivatization. Column switching between ZWIX(+) and ZWIX(-) is believed to be an instrumental tool to reverse or control the enantiomers elution order, due to the complementarity of the applied chiral selectors.

Chiral separation of quinolones by liquid chromatography and capillary electrophoresis

“…This suggested the researchers to try new materials, such as a hybrid polymeric CSP showing enantioselectivity with respect to various chiral heterocyclic compounds or Chincona alkaloid‐based zwitterionic CSPs. These proved their ability to separate enantiomers of molecules having both free amino and carboxylic groups and enantiomers of quinoline derivatives .…”

Determination of enantiomeric excess of nipecotic acid as 1‐(7‐nitrobenzo[c][1,2,5]oxadiazol‐4‐yl) derivatives

“…9 But this method was only validated for the quantification of (S)-enantiomer in the presence of (R)-enantiomer, but not vice versa. 9 For the chiral separation of underivatized nipecotic acid, methods based on chiral ligand-exchange 16 or zwitterionic chiral stationary phases [17][18][19] have been reported. Because of the absorption wavelength of 230 nm resulting from the carboxylic acid ester function exhibiting a low absorption coefficient, the selectivity and sensitivity of this method is to be regarded as low and thus of limited suitability for the determination of highly enantioenriched samples of the ethyl ester of 1.…”

“…Because of the absorption wavelength of 230 nm resulting from the carboxylic acid ester function exhibiting a low absorption coefficient, the selectivity and sensitivity of this method is to be regarded as low and thus of limited suitability for the determination of highly enantioenriched samples of the ethyl ester of 1. 19 But this approach has the disadvantage that for the analysis, because nipecotic acid (1) is devoid of a chromophore, detectors such as an ELSD (evaporating light scattering detector) or a CAD (corona charged aerosol detector) are required. Considering that only for a resolution of ≥1.5, Gaussian peaks will be baseline separated, 15 a reliable ee determination especially for highly enantioenriched samples appears questionable.…”

A short synthesis ofd-[1-14C]-serine of high enantiomeric purity

“…In the course of our drug discovery research in the central nervous system therapeutic area, radiolabeled d ‐[1‐ 14 C]‐serine with high enantiomeric and chemical purity was urgently needed. Direct resolution of underivatized d / l ‐serine can be achieved by chiral HPLC, however, so far, applications have been limited to analytical scales because of the limitations of chiral column loading capacity on the efficient separation of both d and l forms. To address the larger scale needs for multimegabecquerel amounts, a short asymmetric synthesis was sought that furnishes d ‐[1‐ 14 C]‐serine in high enantiomeric purity and circumvents the scale limiting preparative chiral HPLC resolution step.…”