Anomerization of N-Acetylglucosamine Glycosides Promoted by Dibromomethane and Dimethylformamide

In previous quests to synthesize fragments of tumor-associated carbohydrate antigens (TACAs), we determined that bromoalkyl β glycosides of <i>N</i>-acetylglucosamine were labile and incompatible with some of the synthetic conditions required for the preparation of oligosaccharides. While <i>N</i>-acetylglucosamine chloroalkyl β glycosides are common intermediates for oligosaccharide synthesis, they exhibit poor yields upon subsequent reactions used to introduce the oxyamine required for further conjugation. Thus, we looked to synthesize these TACAs using chloroalkyl β glycosides and substitute the chlorine for bromine at a later synthetic stage. Upon substitution of the bromine for chlorine using sodium bromide in a dibromomethane (DBM) dimethylformamide (DMF) mixture, we observed the unexpected anomerization of the <i>N</i>-acetylglucosamine β glycosides, yielding up to 90% of the α glycosides. We describe our studies of this unexpected anomerization and report on how the anomeric ratios can be controlled experimentally. Interestingly, we also report the anomerization of alkyl β glycosides of <i>N</i>-acetylglucosamine in a mixture of DBM and DMF without sodium bromide. Further studies are being conducted to determine the mechanism of this anomerization and the scope of this reaction.