No abstract

Cinchona-derived anion-exchange-type chiral selectors have been adapted and employed in countercurrent chromatography (CCC) for the separation of enantiomers of N-derivatized amino acids and 2-aryloxypropionic acids. The accurate optimization of the enantioseparation in terms of solvent system composition, pH values, ionic strength, and CCC operating conditions was performed. A wide range of solvent mixtures was evaluated. Successful resolutions were achieved in systems such as ammonium acetate buffer/tert-amyl alcohol/methanol/heptane and especially ammonium acetate buffer/methyl isobutyl ketone or diisopropyl ether. Up to 300 mg (0.92 mmol) of N-(3,5-dinitrobenzoyl)-(+/-)-leucine was totally resolved in a single run using a 10 mM concentration of chiral selector in 122 mL of stationary phase. This amount could be increased up to 900 mg (2.77 mmol) when pH-zone-refining mode was applied. The results here presented account for the high potential of CCC as a preparative enantiomer separation technique.

SummaryAn enantioselective liquid-solid batch extraction method is described for the screening of novel chiral stationary phases (CSPs) during optimization studies of chiral selectors derived form a common lead structure. Extraction enantioselectivity (a) values can be calculated from the enantiomeric excess ee-values of the selectand, which are measured in the liquid phase by enantioselective HPLC. Extraction e-values have been correlated with chromatographic e-values. The influence was studied of several experimental parameters of the assay (pHa, buffer concentration, temperature, selector/selectand and phase ratio) on the enantiomeric excess (ee) values of the selectands and the enantioselectivity of the CSPs, respectively. The derived statistically significant model has then been implemented to predict chromatographic 0c-values of novel CSPs. For example, an ee of 89.3 % for DNB-Leu as selectand could be achieved in batch extraction for a novel synthesized but mechanistically similarly-acting CSP derived form quinine. This corresponds to a calculated extraction e-value of 17.7. Based Oil this eextraction a chromatographic e-value of 28.8 was predicted by the linear correlation model; the experimental HPLC e-value of 31.7 was in good agreement and demonstrated the validity of the proposed screening method. The method is particularly helpful in SO optimization studies.