'Ab Ovo' Chiral Phases and Chiral Reagents for Liquid Chromatographic Separation and Isolation of Enantiomers

The de-novo approach of mixing chirally pure reagents or Cu(II)-L-amino acid complexes in the slurry of silica gel for preparing TLC plates was reported from author's laboratory and was successful for separation and isolation of enantiomers. Using high molar absorptivity molecules, e.g., 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, more than 38 new chiral derivatizing reagents were synthesized in our laboratory by straightforward nucleophilic substitution with simple chiral auxiliaries. Besides, (S)-naproxen, (S)-ketoprofen, and (S)-levofloxacin were used as chiral platforms. A conceptual approach using both achiral phases in chromatography for enantioseparation was also adopted. H-1 NMR and DFT based software were used to explain structures of non-covalent and covalent diastereomeric pairs and determination of configuration and separation mechanism. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases.

Automated summary

The study successfully separated and isolated enantiomers by using a de-novo approach of mixing chirally pure reagents or Cu(II)-L-amino acid complexes. More than 38 new chiral derivatizing reagents were synthesized in the laboratory, and a conceptual approach using both achiral phases in chromatography for enantioseparation was adopted. H-1 NMR and DFT based software were used to explain structures, determine configuration and separation mechanisms.