Facile synthesis of pseudo-C-glycosyl p-amino-dl-phenylalanine building blocks via Amadori rearrangement

We studied the synthesis of pseudo-C-glycosyl amino acid via an Amadori rearrangement in aqueous solution using unprotected d-lactose and a tyrosine analogue: the p-amino-dl-phenylalanine. Two steps were necessary. In the first step, the N-glycosylation of d-lactose was carried out in aqueous conditions. The synthesized N-glycosylamine was stabilized in a second step by the formation of Amadori compound, the N-[β-d-galactosyl-1-4-(1-deoxyfructos-1-yl)]-p-amino-dl-phenylalanine. Products were purified and characterized by mass spectrometry and by 1H and 13C NMR. The influence of the temperature, the pH, the nature of acid and the concentration of the acid on the synthesis yield was examined in order to determine the optimum conditions of Amadori rearrangement. In the best conditions, 35% of p-amino-dl-phenylalanine was converted into N-[β-d-galactosyl-1-4-(1-deoxyfructos-1-yl)]-p-amino-dl-phenylalanine. For the N-glycosylation, a specific base catalysis took place in the media whereas a general acid catalysis was observed for the Amadori rearrangement using weak acids and with a temperature close to 75 °C. The Amadori compound from glucose [N-(1-deoxyfructopyranos-1-yl)-p-amino-dl-phenylalanine] was also synthesized and characterized by mass spectrometry and by 1H and 13C NMR.