title: Conformationally armed 3,6-tethered glycosyl donors: synthesis, conformation, reactivity, and selectivity.
abstract: The reactivity and selectivity of 3,6-tethered glycosyl donors have been studied using acceptors with different steric and electronic characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl donors were synthesized in high yields from their common parent sugars. The glycosylation properties were tested using at least three different acceptors and several promoter systems. Thiophenyl 2,4-di-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-D-glucopyranoside gave α/β mixtures with standard NIS/TfOH mediated activation, whereas the corresponding fluoride was found to be highly β-selective, when using SnCl2/AgB(C6F5)4 as the promoter system. Mannosyl donors were highly α-selective despite the altered conformation. Galactosylations using NIS/TfOH were generally α-selective, but more β-selective using the galactosyl fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-D-glucopyranoside was found to be α-selective. The reactivity of the donors was investigated using competition experiments, and some but not all were found to be highly reactive. Generally it was found that the α-thioglycosides were significantly more reactive than the β; this difference in reactivity was not found for 3,6-anhydro-, armed-(benzylated), or the classic super armed (silylated) donors. A mechanism supporting the unusual observations has been suggested.
authors.affiliation: Department of Chemistry, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Heuckendorff
authors.forename: Christian Marcus
authors.initials: CM
authors.lastname: Pedersen
authors.forename: Mikael
authors.initials: M
authors.lastname: Bols
mesh_terms: D002236:Carbohydrate Conformation; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation
chemical_list: D006027:Glycosides