Facile determination of the absolute configurations of alpha-hydroxy acids by chiral derivatization coupled with liquid chromatography-mass spectrometry analysis

Abstract

alpha-Hydroxy acids are commonly encountered in natural bioactive molecules. For convenient determination of the absolute configurations of alpha-hydroxy acids, a simple method, named the "O-Marfey method" was developed using a chiral derivatization strategy with (1-fluoro-2,4-dinitrophenyl-5)-L-alanine amide (L-FDAA). The liquid chromatography-mass spectrometry (LC-MS) analysis of the derivatives clearly determined the absolute configurations of various alpha-hydroxy acids based on their elution times and sequences. This new method is operationally simple with short reaction time and sensitive enough for application at a sub-milligram scale without any purification. This method also enables the simultaneous chirality analysis of alpha-hydroxy acids and alpha-amino acids. The absolute configuration of a natural depsipeptide bearing an alpha-hydroxy acid and alpha-amino acids was successfully determined by our O-Marfey application. (C) 2012 Elsevier B.V. All rights reserved.