Enantioseparation of chiral (benzylsulfinyl)benzamide sulfoxides by capillary electrophoresis using cyclodextrins as chiral selectors

Sulfur as a stereogenic center can be found in synthetic compounds and natural products. The current study evaluated the enantioseparation of 16 chiral (benzylsulfinyl)benzamide compounds by capillary electrophoresis using charged cyclodextrins (CDs) as chiral selectors in 50 mM sodium acetate buffer, pH 5.5. The sulfoxides varied in the type and position of the substituent of the benzyl moiety as well as the position and methylation of the amide group. Typically, randomly substituted CDs separated the majority of the model analytes in contrast to single isomer CDs. In case of random substitution, gamma-CD derivatives displayed higher resolution ability toward the set of model compounds followed by beta-CD and alpha-CD derivatives. Except for a few examples, the ( + )-enantiomer of the analytes migrated before the (-)-isomer irrespective of the type of the CD so that the chiral recognition appeared to be also mostly independent on the structure of the sulfoxides. Evaluation of complexation constants and complex mobilities of selected CD-analyte pairs revealed that the separations were based on the stereoselective complexation by the CD expressed as complexation constants but examples for complex mobilities as the determining factor for the enantiomer migration order were also found. In case of 2-(4-bromobenzylsulfinyl)-N-methyl benzamide in the presence of heptakis(2,3-di-O-methyl-6-O-sulfo)-alpha-CD reversal of the enantiomer migration order as a function of the CD concentration was observed. Using neutral CD derivatives in the presence of sodium dodecyl sulfate-based micelles at pH 9.0 only few sulfoxides could be enantioseparated. (C)& nbsp;2022 Elsevier B.V. All rights reserved.

Automated summary

This study evaluated the enantioseparation of 16 chiral compounds using capillary electrophoresis with charged cyclodextrins as chiral selectors. It found that randomly substituted cyclodextrins showed good separation ability for the model analytes. The study also discovered the influence of complexation constants and complex mobilities on the migration order of enantiomers.