title: Stereochemistry of intramolecular cyclization of tetra-β-(1→6)-D-glucosamines and related tetrasaccharides: the role of the conformational stereocontrol and the neighboring group participation.
abstract: The effect of reaction conditions, the nature of a leaving group, and a substituent at C-2 in the glycosylating monosaccharide on the stereochemical outcome of cyclization of linear tetra-β-(1→6)-d-glucosamines and some 'mixed' tetrasaccharides comprising glucose and glucosamine residues has been examined. Toluene and nitrile solvents improved the β-stereoselectivity of cyclization, however, the overall efficiency of the formation of cyclic products in these solvents was lower than that in dichloromethane. The use of bromide or pentenyl glycoside as leaving groups instead of the thioglycoside did not increase the β-stereoselectivity. Replacement of the N-phthaloyl group in the glycosylating unit by N-Troc one did not affect the stereoselectivity of cyclization, while the tetrasaccharides, which contained 2-O-benzoyl glucose instead of glucosamine as the glycosyl donor moiety, were found to provide β-linked cyclic products exclusively. Using this finding, two cyclic tetrasaccharides with alternate or adjacent arrangement of two glucose and two glucosamine units have been efficiently synthesized. These cycles were intended for the preparation of divalent glycoclusters with different ligand orientation. The difference in the stereoselectivity of cyclization of glucose and glucosamine precursors was accounted for by more effective anchimeric participation of the O-benzoyl group as compared to N-Phth and N-Troc counterparts that was confirmed by calculations of the stabilization energy and rotational barriers around C2-O/N bond in the corresponding glycosyl cations. Only the 2-O-benzoylated glycosyl cation proved to be able to form a stabilized dioxalenium intermediate, which provides stereospecific β-glycosylation.
authors: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia.
authors: Denis V
authors: DV
authors: Titov
authors: Marina L
authors: ML
authors: Gening
authors: Alexey G
authors: AG
authors: Gerbst
authors: Alexander O
authors: AO
authors: Chizhov
authors: Yury E
authors: YE
authors: Tsvetkov
authors: Nikolay E
authors: NE
authors: Nifantiev
mesh_terms: D002236:Carbohydrate Conformation; D000075202:Contraindications; D003500:Cyclization; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D009844:Oligosaccharides; D005944:Glucosamine
keywords: Anchimeric participation; Conformational stereocontrol; Cyclic oligosaccharides; Intramolecular glycosylation, stereoselectivity; Oligo-β-(1→6)-d-glucosamines, cyclic