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 beta-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 beta-N-glycosyl- para-amino-phenyl alanine building blocks for the tumor- associated carbohydrate antigen (TACA) glycopeptides synthesis. Analysis of products by H-1 and C-13 NMR indicated that the Amadori rearrangement had not occurred after formation of the stereoselective beta-N-glycoside bond (natural N-glycoprotein linkage). The study of the chemical and enzymatic stability in aqueous media of beta-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-glycosidie 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. (C) 2007 Elsevier Ltd. All rights reserved.