The enantiomeric separation of 4,5-disubstituted imidazoles by HPLC and CE using cyclodextrin-based chiral selectors

Abstract

The enantiomeric separation of a series of fifteen racemic 4,5-disubstituted imidazole compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). These alkaloid analytes are important precursors for the total synthesis of the natural product calcaridine A and other Leucetta-derived alkaloids. Therefore, the enantiomeric analysis of these analytes is not only important in the production of enantiomerically pure calcaridine A, but also for a better understanding of the stereochemistry involved in related biosynthetic pathways. Several bonded cyclodextrin (both native and derivatised) stationary phases were evaluated for their ability to separate these racemates via HPLC. Likewise, several cyclodextrin derivatives were evaluated for their ability to separate this set of compounds via CE. Using HPLC, 14 of the 15 racemic compounds were separated. Eight of the analytes were separated using CE with resolutions up to 7.0. Using both HPLC and CE approaches, the entire set of analytes was separated. The optimisation of these separations was discussed and a comparison between the chiral selectors used was made. Lastly, the similarity of the 15 analytes allowed for insight into the mechanism of chiral recognition.

Keywords:

• enantiomeric separations
• chiral separations
• high performance liquid chromatography
• capillary electrophoresis
• cyclodextrin
• calcaridine A

Acknowledgements

We gratefully acknowledge the National Institute of Health (NIH 5 R01-GM53825-13) and NIH GM065503) and the Welch foundation (Welch Y-1362) for their financial support of this work.