Application of hydrophilic interaction liquid chromatography/comparative taste dilution analysis for identification of a bitter inhibitor by a combinatorial approach based on Maillard reaction chemistry

Activity-directed fractionation of heated carbohydrate/alanine solutions recently led to the discovery of (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2- (hydroxymethyl)pyridinium inner salt (1, alapyridaine), and it has been shown that this compound lowers the detection thresholds of sugars, glutamate, and NaCl solutions, whereas no influence on bitter perception was observed. As this class of Maillard-derived pyridinium betaines seemed to be promising targets for further research on their taste modulatory activity, the objective of the present investigation was to screen for bitter taste-suppressing target molecules in combinatorial libraries of pyridinium betaines prepared from 5-(hydroxymethyl)-furan-2-aldehyde and amino acid mixtures by use of Maillard-type reaction chemistry instead of synthesizing and purifying each derivative individually. By application of hydrophilic interaction liquid chromatography in combination with the recently developed comparative taste dilution analysis, followed by structure determination, synthesis, and sensory studies, we have now succeeded in identifying 1-carboxymethyl-5-hydroxy-2- hydroxymethylpyridinium inner salt (2) as a potential bitter-suppressing candidate. While tasteless on its own, 2 was found to reduce the bitterness of various bitter tastants such as the amino acid L-phenylalanine, the peptide Gly-Leu, the alkaloid caffeine, and the bitter glycosides salicin and naringin.