title: Mapping the Reactivity and Selectivity of 2-Azidofucosyl Donors for the Assembly of N-Acetylfucosamine-Containing Bacterial Oligosaccharides.
abstract: The synthesis of complex oligosaccharides is often hindered by a lack of knowledge on the reactivity and selectivity of their constituent building blocks. We investigated the reactivity and selectivity of 2-azidofucosyl (FucN3) donors, valuable synthons in the synthesis of 2-acetamido-2-deoxyfucose (FucNAc) containing oligosaccharides. Six FucN3donors, bearing benzyl, benzoyl, or tert-butyldimethylsilyl protecting groups at the C3-O and C4-O positions, were synthesized, and their reactivity was assessed in a series of glycosylations using acceptors of varying nucleophilicity and size. It was found that more reactive nucleophiles and electron-withdrawing benzoyl groups on the donor favor the formation of β-glycosides, while poorly reactive nucleophiles and electron-donating protecting groups on the donor favor α-glycosidic bond formation. Low-temperature NMR activation studies of Bn- and Bz-protected donors revealed the formation of covalent FucN3triflates and oxosulfonium triflates. From these results, a mechanistic explanation is offered in which more reactive acceptors preferentially react via an SN2-like pathway, while less reactive acceptors react via an SN1-like pathway. The knowledge obtained in this reactivity study was then applied in the construction of α-FucN3linkages relevant to bacterial saccharides. Finally, a modular synthesis of the Staphylococcus aureus type 5 capsular polysaccharide repeating unit, a trisaccharide consisting of two FucNAc units, is described.
authors.affiliation: Leiden Institute of Chemistry, Universiteit Leiden , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Hagen
authors.affiliation: Leiden Institute of Chemistry, Universiteit Leiden , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Ali
authors.affiliation: Leiden Institute of Chemistry, Universiteit Leiden , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Leiden Institute of Chemistry, Universiteit Leiden , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Leiden Institute of Chemistry, Universiteit Leiden , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Jeroen D C
authors.identifier: 0000-0003-3531-2138
authors.initials: JD
authors.lastname: Codée
mesh_terms: D002240:Carbohydrate Sequence; D005643:Fucose / Q000031:analogs & derivatives* / Q000737:chemistry; D006031:Glycosylation; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013211:Staphylococcus aureus / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D009844:Oligosaccharides; D005643:Fucose; C059377:N-acetylfucosamine