- Binding of the Bacterial Adhesin FimH to Its Natural, Multivalent High-Mannose Type Glycan Targets
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Multivalent carbohydrate-lectin interactions at host-pathogen interfaces play a crucial role in the establishment of infections. Although competitive antagonists that prevent pathogen adhesion are promising antimicrobial drugs, the molecular mechanisms underlying these complex adhesion processes are still poorly understood. Here, we characterize the interactions between the fimbrial adhesin FimH from uropathogenic Escherichia coli strains and its natural high-mannose type N-glycan binding epitopes on uroepithelial glycoproteins. Crystal structures and a detailed kinetic characterization of ligand-binding and dissociation revealed that the binding pocket of FimH evolved such that it recognizes the terminal α(1-2)-, α(1-3)-, and α(1-6)-linked mannosides of natural high-mannose type N-glycans with similar affinity. We demonstrate that the 2000-fold higher affinity of the domain-separated state of FimH compared to its domain-associated state is ligand-independent and consistent with a thermodynamic cycle in which ligand-binding shifts the association equilibrium between the FimH lectin and the FimH pilin domain. Moreover, we show that a single N-glycan can bind up to three molecules of FimH, albeit with negative cooperativity, so that a molar excess of accessible N-glycans over FimH on the cell surface favors monovalent FimH binding. Our data provide pivotal insights into the adhesion properties of uropathogenic Escherichia coli strains to their target receptors and a solid basis for the development of effective FimH antagonists.
- Sauer, Maximilian M.,Jakob, Roman P.,Luber, Thomas,Canonica, Fabia,Navarra, Giulio,Ernst, Beat,Unverzagt, Carlo,Maier, Timm,Glockshuber, Rudi
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supporting information
p. 936 - 944
(2019/01/11)
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- Synthesis and structural investigation of a series of mannose-containing oligosaccharides using mass spectrometry
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A series of compounds associated with naturally occurring and biologically relevant glycans consisting of α-mannosides were prepared and analyzed using collision-induced dissociation (CID), energy-resolved mass spectrometry (ERMS), and 1H nucle
- Daikoku,Pendrill,Kanie,Ito,Widmalm,Kanie
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p. 228 - 238
(2018/01/12)
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- Synthesis and binding affinity analysis of α1-2- and α1-6-O/S-linked dimannosides for the elucidation of sulfur in glycosidic bonds using quartz crystal microbalance sensors
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The role of sulfur in glycosidic bonds has been evaluated using quartz crystal microbalance methodology. Synthetic routes towards α1-2- and α1-6-linked dimannosides with S- or O-glycosidic bonds have been developed, and the recognition properties assessed in competition binding assays with the cognate lectin concanavalin A. Mannose-presenting QCM sensors were produced using photoinitiated, nitrene-mediated immobilization methods, and the subsequent binding study was performed in an automated flow-through instrumentation, and correlated with data from isothermal titration calorimetry. The recorded Kd-values corresponded well with reported binding affinities for the O-linked dimannosides with affinities for the α1-2-linked dimannosides in the lower micromolar range. The S-linked analogs showed slightly disparate effects, where the α1-6-linked analog showed weaker affinity than the O-linked dimannoside, as well as positive apparent cooperativity, whereas the α1-2-analog displayed very similar binding compared to the O-linked structure.
- Norberg, Oscar,Wu, Bin,Thota, Niranjan,Ge, Jian-Tao,Fauquet, Germain,Saur, Ann-Kathrin,Aastrup, Teodor,Dong, Hai,Yan, Mingdi,Ramstr?m, Olof
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supporting information
p. 35 - 42
(2017/10/25)
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- Completely β-selective glycosylation using 3,6- O-(o-xylylene)-bridged axial-rich glucosyl fluoride
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A completely β-selective glycosylation that does not rely on neighboring group participation is described. The novelty of this work is the design of the glycosyl donor locked into the axial-rich form by the o-xylylene bridge between the 3-O and 6-O of d-glucopyranose. The synthesized 2,4-di-O-benzyl-3,6-O-(o-xylyene)glucopyranosyl fluoride could efficiently react with various alcohols in a SnCl2-AgB(C6F 5)4 catalytic system. The mechanism composed of the glycosylation and isomerization cycles was revealed through comparative experiments using acidic and basic molecular sieves. The achieved perfect stereocontrol is attributed to the synergy of the axial-rich conformation and convergent isomerization caused by HB(C6F5)4 generated in situ.
- Okada, Yasunori,Asakura, Noriaki,Bando, Masafumi,Ashikaga, Yoshiki,Yamada, Hidetoshi
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p. 6940 - 6943
(2012/06/15)
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- A fluorous-assisted synthesis of oligosaccharides using a phenyl ether linker as a safety-catch linker
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We report on the fluorous-assisted synthesis of oligosaccharides using a phenyl ether linker. The phenyl ether linker is stable under both acidic and basic conditions but can be cleaved under mildly acidic conditions after reduction to a vinyl ether. The utility of the method was demonstrated by the synthesis of a trisaccharide. A protected trisaccharide with a light-fluorous tag was directly prepared by one-pot glycosylation using three building blocks that contained a building block with a light-fluorous tag though a phenyl ether. A Birch reduction of the trisaccharide provided a fully deprotected trisaccharide with the fluorous tag attached through a vinyl ether, which was easily purified by solid-phase extraction. The tag was cleaved from the sugar portion by treatment with 3% TFA in MeOH.
- Tanaka, Hiroshi,Tanimoto, Yosuke,Kawai, Tetsuya,Takahashi, Takashi
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experimental part
p. 10011 - 10016
(2012/02/05)
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- Conformational flexibility and dynamics of two (1→6)-Linked disaccharides related to an oligosaccharide epitope expressed on malignant tumour cells
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The conformational flexibility and dynamics of two (1→6)-linked disaccharides that are related to the action of the glycosyl transferase GnT-V have been investigated. NMR NOE and T-ROE spectroscopy experiments, conformation-dependent coupling constants an
- Olsson, Ulrika,Saewen, Elin,Stenutz, Roland,Widmalm, Goeran
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experimental part
p. 8886 - 8894
(2010/07/04)
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- How the arming participating moieties can broaden the scope of chemoselective oligosaccharide synthesis by allowing the inverse armed-disarmed approach
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(Chemical Equation Presented) A new method for stereocontrolled glycosylation and chemoselective oligosaccharide synthesis has been developed. It has been determined that complete 1,2-trans selectivity can be achieved with the use of a 2-O-picolyl moiety,
- Smoot, James T.,Demchenko, Alexei V.
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experimental part
p. 8838 - 8850
(2009/04/05)
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- Development of an arming participating group for stereoselective glycosylation and chemoselective oligosaccharide synthesis
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(Chemical Equation Presented) Armed and dangerous: A new armed-disarmed glycosylation strategy (see picture) allows chemoselective introduction of a 1,2-trans glycosidic linkage prior to other linkages through the use of a 2-O-picolyl moiety. This neighbo
- Smoot, James T.,Pornsuriyasak, Papapida,Demchenko, Alexei V.
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p. 7123 - 7126
(2007/10/03)
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- Removal of benzyl protecting groups from controlled pore glass linked sugars
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Removal of benzyl protecting groups from controlled pore glass bound monosaccharides can be performed with the NaBrO3/Na2S2O4 system in ethyl acetate/water.
- Adinolfi, Matteo,Barone, Gaspare,Iadonisi, Alfonso,Schiattarella, Marialuisa
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p. 5971 - 5972
(2007/10/03)
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- Transglycosylation reactions with a crude culture filtrate from Thermoascus aurantiacus
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Some characteristics of regioselectivity and acceptor tolerance in transglycosylation reactions, catalysed by a crude culture filtrate from Thermoascus aurantiacus, were examined by employing methanol and monosaccharides as acceptors. When β-D-mannopyranosyl fluoride was employed as the donor, the anomeric configuration of the newly formed bond was found to depend on the structure of the acceptor used. Copyright (C) 2000 Elsevier Science Ltd.
- Ortner, Joerg,Albert, Martin,Terler, Katherine,Steiner, Walter,Dax, Karl
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p. 483 - 487
(2007/10/03)
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- Efficient Intramolecular Glycosylation Supported by a Rigid Spacer
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The m-xylylene moiety was employed as rigid spacer in intramolecular glycoside bond formation. Fifteen-membered macrocycle formation starting from 6-O-linked donor and 6- and 4-O-linked acceptor (5a,b, 6b) led exclusively to β(1-4)- and β(1-6)-linked compounds 7β and 8β, respectively, which gave cellobioside and gentiobioside derivatives. The glycosylation yields could be improved by 14-membered macrocycle formation. In the four cases studied, the donor was 6-O-linked to the spacer. For the acceptor linkage to the spacer and the accepting hydroxy group, relative D-/L-threo- and D-/L-erythro-arrangements were chosen. Standard glycosylation conditions led in three cases (13, 14, 23) only to β-linkage in high yield (16β, 17β, 25β). For the transformation of 24, having a D-erythro-arrangement in the acceptor moiety, the α-anomer 26α was preferentially obtained. Limitation of the conformational space of the donor and the acceptor as in 31, which is stereochemically identical with 24, led to the corresponding α-glycoside 32α in 87% yield. Synthesis of a pseudo mirror image of 23 [having 6-(D)/3-(D-threo)-arrangement], namely 35, having 3(L)/6-(L-threo)-arrangement of the donor and acceptor moieties, expectedly gave only α-glycoside 36α in very high yield. Thus, the efficiency and versatility of this conceptual approach to intramolecular glycoside bond formation is exhibited.
- Mueller, Matthias,Huchel, Ursula,Geyer, Armin,Schmidt, Richard R.
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p. 6190 - 6201
(2007/10/03)
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- Use of controlled pore glass in solid phase oligosaccharide synthesis. Application to the semiautomated synthesis of a glyconucleotide conjugate
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Three polymetric supports (polystyrene. Tentagel and controlled pore glass) have been tested for solid phase synthesis of oligosaccharides based on the trichlorocctimidate methodology. Controlled pore glass has been found to yield satisfactory results wit
- Adinolfi, Matteo,Barone, Gaspare,De Napoli, Lorenzo,Iadonisi, Alfonso,Piccialli, Gennaro
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p. 1953 - 1956
(2007/10/03)
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- Synthesis and semisynthesis of some structural elements of oligo-mannose type N-glycoproteins
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For the construction of N-glycoprotein glycan chains, valuable potential glycosyl donors, O-α-D-mannopyranosyl-(1→2)-α-D-mannopyranose octaacetate (19) and O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→2)- α-D-mannopyranose undecaacetate (20) were ob
- Szurmai, Zoltan,Janossy, Lorant,Szilagyi, Zoltan,Vekey, Karoly
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p. 417 - 437
(2007/10/03)
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- A SIMPLE STRATEGY FOR CHANGING THE REGIOSELECTIVITY OF GLYCOSIDASE-CATALYSED FORMATION OF DISACCHARIDES
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The regioselectivity of glycosidase-catalysed formation of disaccharides can be changed by using α- or β-glycosyl acceptors with various aglycons.The preponderant formation of other than (1->6) linkages can be effected with glycosidases which normally give (1->6) linkages.Thus, an α-D-galactosidase can be induced to catalyse the formation mainly of α-(1->2)-, α-(1->3)-, or α-(1->6)-linked digalctosides.Both the structure of the aglycon and the configuration of the glycosidic linkage can have a pronounced influence on the regioselectivity of disaccharide formation.Enzymic syntheses, in yields of 20-30percent, are described of α-D-Galp-(1->3)-α-D-Galp-OMe, β-D-Galp-(1->3)-β-D-Galp-OMe, β-D-Galp-(1->6)-α-D-Galp-OMe, α-D-Manp-(1->2)-α-D-Manp-OMe, α-D-Manp-(1->6)-α-D-Manp-OMe, α-D-Galp-(1->2)-α-D-Galp-OPhNO2-o, α-D-Galp-(1->3)-α-D-Galp-OPhNO2-p, α-D-Manp-(1->2)-α-D-Manp-OPhNO2-p, and α-D-Manp-(1->2)-α-D-Manp-(1->2)-α-D-Manp-OMe.Soluble and immobilised enzymes have been used.
- Nilsson, Kurt G. I.
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- LYSOSOMAL-ENZYME TARGETING: THE PHOSPHORYLATION OF SYNTHETIC D-MANNOSYL SACCHARIDES BY UDP-N-ACETYLGLUCOSAMINE:LYSOSOMAL-ENZYME N-ACETYLGLUCOSAMINE-PHOSPHOTRANSFERASE FROM RAT-LIVER MICROSOMES AND FIBROBLASTS
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Phosphorylation of the D-mannose residues of lysosomal-enzymes is essential for the uptake and intracellular transport of these enzymes to lysosomes.The GlcNAc-P-transferase which is involved in the phosphorylation reaction seems to recognize a signal, probably a protein conformation, common to many lysosomal enzymes.To evaluate the role of the carbohydrate portion of the enzyme in these phosphorylation reactions, the acceptor specificity of GlcNAc-P-transferase from rat-liver microsomes and fibroblasts was examined with the aid of synthetic D-mannosyl disaccharides and derivatives that are closely related to the high-mannose type of oligosaccharides.Four methyl D-mannobiosides were synthesized, and their structures were established by 13C-n.m.r. spectroscopy.Of all the D-mannosyl saccharides tested, α-D-Man-(1->2)-α-D-Man-(1->OMe) was found to be the best acceptor, thereby suggesting that oligosaccharide structure may also have a role to play in recognition by this enzyme.
- Madiyalakan, Ragupathy,Chowdhary, Manjit S.,Rana, Surjit S.,Matta, Khushi L.
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p. 183 - 194
(2007/10/02)
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- Nuclear Magnetic Resonance Studies of 1,6-Linked Disaccharides
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The signals in the (13)C n.m.r. spectra of all anomeric forms of the methyl glycosides of D-Glcp-(1-->6)-D-Glcp and D-Glcp-(1-->6)-D-Galp in water have been assigned.The chemical-shift differences obtained by comparison with relevant monosaccharide derivatives were used to calculate (13)C n.m.r. spectra of oligo- and poly-saccharides containing 1,6-linkages.Good agreement between calculated and experimental spectra were obtained for raffinose, stachyose, dextran, and pustulan.The importance of comparing spectra determined at the same temperature is emphasized.Temperature shifts may, in favourable cases, be used for assignment of signals.
- Forsgren, Marianne,Jansson, Per-Erik,Kenne, Lennart
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p. 2383 - 2388
(2007/10/02)
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- A NOVEL OBSERVATION ON KOENIGS-KNORR CONDENSATION OF 2,3,4,6-TETRA-O-ACETYL-α-D-GLUCOPYRANOSYL BROMIDE WITH METHYL 4,6-O-BENZYLIDENE-α-D-GLUCOPYRANOSIDE
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As a result of condensation between methyl 4,6-O-benzylidene-α-D-glucopyranoside and bromo-2,3,4,6-tetra-O-acetyl-α-D-glucopyranose in 1,2-dichloroethane in presence of silver carbonate, after removal of functional groups, the following substances were ob
- Temeriusz, Andrzej,Piekarska, Boguslawa,Radomski, Jan,Stepinski, Janusz
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p. 141 - 147
(2007/10/02)
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- Syntheses of model oligosaccharides of biological significance. Synthesis of methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-d-mannopyranoside and the corresponding mannobiosides.
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Methyl 2-O-allyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl) -alpha-D-mannopyranoside (12) was prepared in 90% yield by Helferich glycosylation of methyl 2-O-allyl-4,6-O-benzylidene-alpha-D-mannopyranoside (9) with tetra-O-acetyl
- Winnik,Brisson,Carver,Krepinsky
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- PREPARATION OF α AND Β ANOMERS OF VARIOUS ISOMERIC METHYL O-D-GALACTOPYRANOSYL-D-GALACTOPYRANOSIDES. STANDARDS FOR INTERPRETATION OF 13C-N.M.R. SPECTRA OF D-GALACTOPYRANANS
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The four isomer of methyl O-β-D-galactopyranosyl-β-D-galactopyranoside were prepared by condensation of 2,3,4,6-tetra-O-acetyl-α-galactopyranosyl bromide with appropriate, partially O-substitued derivatives of methyl β-D-galactopyranoside.Reaction of 3,4,6-tri-O-acetyl-1,2-O-(1-ethoxyethylidene)-α-D-galactopyranose with the same acceptors, in the presence of mercuric bromide, led to the formation of α and β linkages.Thus, it was possible to assign 13C-n.m.r. resonances of α and β anomers of methyl O-D-galactopyranosyl-β-D-galactopyranosides.In terms of application of these shift values and those of related D-galactobioses to the structual analysis of D-galactopyranans by shift comparisons, some generalizations can be made.For β-D-galactopyranans, the resonances glycosyloxylated carbon atoms of methyl O-β-D-galactopyranosyl-β-D-galactopyranosides are sensitive to structure and appear to have typical values, whereas limited variation was observed with shift of C-1' signals.On the other hand, for assigning structures to D-galactopyranans containing α linkages, the C-1' shifts (at higher field) of methyl O-α-D-galactopyranosyl-β-D-galactopyranosidesc are sensitive to linkage position, whereas those of glycosyloxylated carbon atoms vary only a little.
- Gorin, Philip A. J.
-
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- RECONSTRUCTION OF GLYCAN CHAINS OF GLYCOPROTEIN BRANCHING MANNOPENTAOSIDE AND MANNOHEXAOSIDE
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Synthetic routes to the branching mannopentaoside 4 and mannohexaoside 5 are described employing properly protected mannobioside 13 as a key intermediate.
- Ogawa, Tomoya,Sasajima, Kikuo
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p. 2787 - 2792
(2007/10/02)
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- SYNTHESIS OF A BRANCHED D-MANNOPENTAOSIDE AND A BRANCHED D-MANNOHEXAOSIDE: MODELS OF THE INNER CORE OF CELL-WALL GLYCOPROTEINS OF Saccharomyces cerevisiae
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Synthetic routes are discussed to the branched D-mannopentaoside methyl 6-O-(2,6-di-O-α-D-mannopyranosyl-α-D-mannopyranosyl)-3-O-α-D-mannopyranosyl-α-D-mannopyranoside and D-mannohexaoside methyl 6-O-(2,6-di-O-α-D-mannopyranosyl-α-D-mannopyranosyl)-3-O-(2
- Ogawa, Tomoya,Sasajima, Kikuo
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p. 231 - 240
(2007/10/02)
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- SYNTHESIS OF A BRANCHED D-MANNOPENTAOSIDE AND A BRANCHED D-MANNOHEXAOSIDE: MODELS OF THE OUTER CHAIN OF THE GLYCAN OF SOYBEAN AGGLUTININ
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Synthetic routes are described to the D-mannopentaoside methyl 3-O-(3,6-di-O-α-D-mannopyranosyl-α-D-mannopyranosyl)-6-O-α-D-mannopyranosyl-α-D-mannopyranoside and the D-mannohexaoside methyl 3-O-(3,6-di-O-α-D-mannopyranosyl-α-D-mannopyranosyl)-6-O-(2-O-α-
- Ogawa, Tomoya,Sasajima, Kikuo
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- SYNTHESIS OF α- AND β-GLYCOPYRANOSIDES via 1-O-ALKYLATION
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1-O-Alkylation of partly protected glucopyranose 1 and galactopyranose 13 led to a convenient, short term synthesis of β-glycosides and β-disaccharides 4a-d and 14.Glucopyranose 2 with a bulky protective group at O-6 yielded exclusively the α-anomer (isomaltoside derivative) 5.
- Schmidt, R. R.,Moering, U.,Reichrath, M.
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p. 3565 - 3568
(2007/10/02)
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