One-pot stereoselective synthesis of β-N-aryl-glycosides by N-glycosylation of aromatic amines: application to the synthesis of tumor-associated carbohydrate antigen building blocks

We studied the stereoselective synthesis of several β-N-aryl-glycosides by glycosylation of aromatic primary amines using unprotected carbohydrates in aqueous solution. This was the first report showing an efficient method for the synthesis with one step of β-N-glycosyl-para-amino-phenyl alanine building blocks for the tumor-associated carbohydrate antigen (TACA) glycopeptides synthesis. Analysis of products by 1H and 13C NMR indicated that the Amadori rearrangement had not occurred after formation of the stereoselective β-N-glycoside bond (natural N-glycoprotein linkage). The study of the chemical and enzymatic stability in aqueous media of β-N-aryl-glycosides synthesized was also investigated. For the first time we have shown that the N-glycosidic bond was relatively stable at pH near to 7 and more stable than the O-glycosidic bond to enzymatic hydrolysis. This higher enzymatic and chemical stability of the N-glycosidic bond is essential to envisage further development of stable TACA building blocks.