How the Substituent at O-3 of N-Acetylglucosamine Impacts Glycosylation at O-4: A Comparative Study

An assessment of the relative reactivities of the 4-OH of N-acetylglucosamine acceptors bearing simple protecting groups, beta-linked or alpha-linked D or L sugars at O-3 is presented, using a per-O-acetylated alpha-D-glucosyl trichloroacetimidate donor Under activation by BF3 center dot OEt2. The presence of either an acyl or carbonate protecting group at O-3 did not impact the reactivity at O-4 with all glycosylations proceeding successfully. On the other hand, the presence of peracetylated Sugar sy O-3 of N-acetylglucosamine acceptors did impact the reactivity of the 4-OH. The acceptors with an alpha-D-Man, beta-D-Gal, or beta-D-Gle at O-3 reacted promptly In comparison, the acceptors bearing beta-L-Fuc, alpha-L-Fuc, or alpha-L-Rha underwent glucosylation slowly, and unreacted acceptor was recovered from the reaction mixtures. Systematic searches carried out on the disaccharide acceptors and trisaccharide products carrying either a peracetylated beta-D-Gal or beta-L-Fuc at O-3 of the glucosamine residue Suggest that, for these two acceptors, a conformational reorientation necessary around the fucosidic linkage contributes to the lower reactivity of the beta-fucosylated acceptor. The acceptors bearing it beta-linked D-Gal, D-Glc, or L-Fuc residue at O-3 each gave trisaccharide products that were mostly stable in the reaction conditions. In contrast, the alpha-linked residues at O-3 were rather unstable in these reaction conditions and the degradation of either the acceptors or trisaccharide products led to low glycosylation yields. In these later reactions, it was impossible to clearly assess which of the acceptor or product underwent degradation its comigration and detection issues prevented us from following these glycosylations by TLC or RP-H PLC. In contrast, the glycosylation of in acceptor carrying an alpha-linked perbenzylated L-Fuc residue at O-3 could be easily monitored by RP-HPLC. The data obtained when monitoring this glycosylation showed that the acceptor underwent prompt glycosylation buta decrease in the absorbance peak corresponding to the trisaccharide along with the appearance of a peak corresponding to it perbenzylated fucose hemiacetal indicated that the trisaccharide product was unstable in the reaction conditions.