title: A protocol for metal triflate catalyzed direct glycosylations with GalNAc 1-OPiv donors.
abstract: Herein we report on the development of novel glycosylation methodology for the concise synthesis of naturally occurring glycoconjugate motifs containing N-acetylgalactosamine (GalNAc) from the cheaper and commercially available N-acetylglucosamine (GlcNAc). The stereoselective glycosylations proceed with catalytic amounts of a promoter and without the need for N-protection other than the biologically relevant N-acetyl group. Among the catalysts explored, both Bi(OTf)3 and Fe(OTf)3 were found to be highly active Lewis acids for this reaction. It was also found that other less reactive metal triflates such as those of Cu(II) and Yb(III) can be beneficial in glycosylation reactions on more demanding glycosyl acceptors. We have furthermore demonstrated that it is possible to control the anomeric stereoselectivity in the glycosylation via postglycosylation in situ anomerization to obtain good yields of α-galactosides. The present protocol was used to prepare important naturally occurring carbohydrate motifs, including a trisaccharide fragment of the naturally occurring marine sponge clarhamnoside.
authors.affiliation: Department of Chemistry, Aarhus University , Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Rasmussen
authors.forename: Mikkel H S
authors.initials: MH
authors.lastname: Marqvorsen
authors.forename: Steffan K
authors.initials: SK
authors.lastname: Kristensen
authors.forename: Henrik H
authors.initials: HH
authors.lastname: Jensen
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry*; D002384:Catalysis; D005697:Galactosides / Q000737:chemistry*; D006031:Glycosylation; D058116:Lewis Acids / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D005697:Galactosides; D058116:Lewis Acids; D008698:Mesylates; D008670:Metals; C012077:trifluoromethanesulfonic acid; D000116:Acetylgalactosamine