Quinine as a highly responsive chiral sensor for the 1H and 19F NMR enantiodiscrimination of N-trifluoroacetyl amino acids with free carboxyl functions

Abstract

Hydrogen-bond accepting and enantiodiscriminating abilities of quinine (Qui) have been exploited in the enantiodiscrimination of N-trifluoroacetyl (TFA) derivatives of amino acids by nuclear magnetic resonance (NMR) spectroscopy. ¹H and ¹⁹F NMR resonances of derivatives of alanine, valine, leucine, norvaline, phenylalanine, phenylglycine, methionine, glutamic acid, proline, and tryptophan were well differentiated employing CDCl₃ and/or C₆D₆ as solvent, with Qui acting in some cases not only as enantiodiscriminating agent, but also as solubility promoter. For derivatives soluble in both solvents, the best results were obtained in benzene-d6, with very high nonequivalence values, which were detectable not only starting from very low equimolar concentrations of 0.1 mM, but also in the presence of sub-stoichiometric amounts of Qui. The quality of enantiodifferentiation has been also evaluated by means of the enantioresolution quotient E. The method has been applied to the detection and quantification of mixtures of amino acid derivatives by single point measurements.