A Practical One-Step Synthesis of 1,2-Oxazoline Derivatives from Unprotected Sugars and Its Application to Chemoenzymatic β-N-Acetylglucosaminidation of Disialo-oligosaccharide

A facile and practical method for synthesis of sugar oxazolines (=dihydrooxazoles) from the corresponding N-acetyl-2-amino sugars has been developed by using 2-chloro-1,3-dimethyl-1H-benzimidazol-3-ium chloride (CDMBI) as a dehydrative condensing agent. The intramolecular dehydrative reaction between the 2-acetamido group and the anomeric OH group of unprotected N-acetyl-2-amino sugars took place smoothly in H2O, leading to the formation of a 1,2-oxazoline (=4,5-dihydrooxazole) moiety in good yield. Since the reaction proceeds in H2O without using any protecting groups, the resulting oxazolines can be utilized as effective glycosyl donors for the subsequent enzymatic glycosylation. We have successfully demonstrated a highly efficient chemoenzymatic transglycosylation of a disialo-oligosaccharide moiety to p-nitrophenyl N-acetylglucosaminide catalyzed by a mutant endo-N-acetylglucosaminidase without isolating disialo-oligosaccharide oxazoline as synthetic intermediate.