title: Why Is Direct Glycosylation with N-Acetylglucosamine Donors Such a Poor Reaction and What Can Be Done about It?
abstract: The monosaccharide N-acetyl-d-glucosamine (GlcNAc) is an abundant building block in naturally occurring oligosaccharides, but its incorporation by chemical glycosylation is challenging since direct reactions are low yielding. This issue, generally agreed upon to be caused by an intermediate 1,2-oxazoline, is often bypassed by introducing extra synthetic steps to avoid the presence of the NHAc functional group during glycosylation. The present paper describes new fundamental mechanistic insights into the inherent challenges of performing direct glycosylation with GlcNAc. These results show that controlling the balance of oxazoline formation and glycosylation is key to achieving acceptable chemical yields. By applying this line of reasoning to direct glycosylation with a traditional thioglycoside donor of GlcNAc, which otherwise affords poor glycosylation yields, one may obtain useful glycosylation results.
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Mikkel H S
authors.initials: MH
authors.lastname: Marqvorsen
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pedersen
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Rasmussen
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Steffan K
authors.initials: SK
authors.lastname: Kristensen
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Dahl-Lassen
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Henrik H
authors.identifier: 0000-0003-2738-4502
authors.initials: HH
authors.lastname: Jensen