title: Conformational and electronic effects on the regioselectivity of the glycosylation of different anomers of N-dimethylmaleoyl-protected glucosamine acceptors.
abstract: In a previous paper (Bohn et al., Carbohydr. Res., 2007, 342, 2522) the relative O3/O4 reactivities of both alpha- and beta-methyl glycosides of N-dimethylmaleoyl (DMM) glucosamine acceptors protected at O6 with three different groups were assessed by us, using two glycosyl donors. The alpha-anomers showed preferential or exclusive substitution at O3, whereas the beta-anomers gave preferential or exclusive substitution at O4. A DFT study of analogs of the reported acceptors indicates that whereas the beta-anomers carry the DMM ring parallel to the C2-H2 bond for steric reasons, the alpha-anomers tilt this ring producing a strong hydrogen bond between the H(O)3 and one of the DMM carbonyl groups. In this way, the O3 group becomes more nucleophilic and thus more reactive: both charge and Fukui functions on O3 and O4 in the model compounds support the experimental results. Surprisingly, the previously mentioned hydrogen bond is not the only driving force for the slant of the DMM group: the axial methoxyl group of the alpha-anomers also plays a role. The ease of rotation around the C2-N2 bond for DMM-protected analogs was assessed with different models. MP2 calculations using higher basis sets yield similar relative energy and charge values to those calculated using DFT.
authors.affiliation: Instituto de Química Orgánica y de Síntesis (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 531, 2000, Rosario, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Bohn
authors.forename: María I
authors.initials: MI
authors.lastname: Colombo
authors.forename: Edmundo A
authors.initials: EA
authors.lastname: Rúveda
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Stortz
mesh_terms: D002236:Carbohydrate Conformation; D004583:Electrons; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D012399:Rotation; D013237:Stereoisomerism; D013379:Substrate Specificity; D009626:Terminology as Topic; D013816:Thermodynamics; D054159:Torsion, Mechanical
chemical_list: D005944:Glucosamine; D010100:Oxygen