title: Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?
abstract: Previous static and dynamical density functional theory studies of the 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts has led to an hypothesis that these cations exist in two families of conformers characterized as (2)S(O) and B(2,5), respectively. These families differ by ring inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl-3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the isopropylidene group allows more flexibility, but two families of conformers can be discerned with the monocyclic oxocarbenium ions in the E(3) conformation and the bicyclic dioxolenium ions in the (4)H(5) conformation. Attack on the beta-face of these monocyclic cations is favored by hydrogen bonding and the anomeric effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O-benzylidene protecting groups can be rationalized assuming that the trans-fused 1,3-dioxane ring allows population of only one family of conformers. The combination of hydrogen bonding and conformational changes of the pyranose ring in response to the C-5[bond]O-5[bond]C-1[bond]C-2 torsion angle changes are identified as key factors in stereoselectivity. Based on these observations a strategy to design face discriminated glycosyl donors that exist predominantly in only one family of conformers is proposed.
authors.affiliation: The Institute for Physical and Chemical Research (RIKEN), Wako-shi, 351-01 Saitama, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Nukada
authors.forename: Attila
authors.initials: A
authors.lastname: Bérces
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Whitfield
mesh_terms: D000475:Alkenes / Q000737:chemistry; D002236:Carbohydrate Conformation; D006031:Glycosylation; D008958:Models, Molecular; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D009844:Oligosaccharides; C013658:propylene