19F NMR enantiodiscrimination and diastereomeric purity determination of amino acids, dipeptides, and amines

Abstract

Chiral amino-group compounds are of significance for human health, such as biogenic amino acids (AAs), dipeptides, and even various drugs. Enantiospecific discrimination of these chiral compounds is vital in diagnosing diseases, identifying pathological biomarkers and enhancing pharmaceutical chemistry research. Here, we report a simple and rapid ¹⁹F NMR-based strategy to differentiate chiral AAs, dipeptides, and amines, that were derivatized with (R)-2-(2-fluorophenyl)-2-hydroxyacetic acid ((R)-2FHA). As a result, 19 proteinogenic AAs (37 isomers) as well as Gly could be concurrently resolved. Moreover, various mirror-image dipeptides, such as Ser–His, Leu–Leu, and Ala–Ala, were commendably recognized. Intriguingly, we found that the absolute configuration of AAs in the N-terminus of dipeptides decided the relative ¹⁹F chemical shifts between two enantiomers. Besides, the ability of this method for enantiodiscrimination was further demonstrated by non-AA amines, including aromatic and aliphatic amines, and even amines having chiral centers several carbons away from the amino-group. The structurally similar antibiotics, amoxicillin and ampicillin, were well discriminated. Furthermore, this method accurately determines the de or dr values of non-racemic mixtures. Therefore, our strategy provides an effective approach for ¹⁹F NMR-based enantiodiscrimination and diastereomeric purity determination of amino-group compounds.