- ANTIMICROBIAL VACCINE COMPOSITIONS
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This invention is directed to antimicrobial vaccine compounds and compositions comprising oligosaccharide β-(1→6)- glucosamine groups having from 3 to 12 glucosamine units linked through a linker group to tetanus toxoid wherein the toxoid is primarily in
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Paragraph 0081; 0085
(2021/03/05)
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- LOW CONTAMINANT ANTIMICROBIAL VACCINES
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Disclosed are antimicrobial vaccines comprising oligosaccharide β-(1→6)-glucosamine groups.
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Paragraph 0081; 0085
(2021/05/21)
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- METHODS FOR PROVIDING CONTINUOUS THERAPY AGAINST PNAG COMPRISING MICROBES
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Disclosed are antimicrobial vaccines comprising oligosaccharide β-(1→6)-glucosamine groups.
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Paragraph 0078; 0082
(2021/05/29)
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- Methods for inhibiting biofilm formation
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Disclosed are methods and kits of parts useful in inhibiting biofilm formation in vivo in subjects at risk of developing biofilms. These methods include inhibiting biofilm formation where the extracellular matrix in the biofilm includes poly-β-(1→6)glucos
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Page/Page column 16; 18
(2020/11/23)
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- Ionic-liquid supported rapid synthesis of an: N -glycan core pentasaccharide on a 10 g scale
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A new and efficient Ionic Liquid-Supported Oligosaccharide Synthesis (ILSOS) strategy for an N-linked core pentasaccharide on a 10 g scale is reported. This new ILSOS includes a new spacer for an IL support, a new tagging strategy, and fast, efficient and orthogonal removal of the ionic-liquid support, producing the N-linked core pentasaccharide with direct applicability potential in a short time, with high yield and on a large gram scale.
- Li, Wei,Gao, Yu,Li, Qing,Li, Zhong-Jun
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supporting information
p. 4720 - 4727
(2018/07/06)
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- Synthesis of Azido-Glycans for Chemical Glycomodification of Proteins
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Chemically produced, accurately linkable oligosaccharides are of importance for the synthesis of neo-glycoproteins. On the route to high-mannose type N-glycans, we present a convenient synthesis of several glycans bearing an azide moiety at the reducing end. An azido-glycan core structure as valuable precursor was modified into the protected N-glycan pentasaccharide core structure and the possibility of modular attachment of different antenna was demonstrated through synthesis of a pentamannose donor and glycosylation with the core structure. The azido function allows for chemical ligation with recombinantly modified proteins featuring noncanonical cyclooctyne amino acids, providing access to customized glycopatterns of glycoproteins, e.g., of antibodies that are of high interest for biopharmaceutical applications.
- Wawryszyn, Mirella,Sauter, Paul F.,Nieger, Martin,Koos, Martin R. M.,Koehler, Christine,Luy, Burkhard,Lemke, Edward A.,Br?se, Stefan
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supporting information
p. 4296 - 4305
(2018/08/29)
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- Synthesis of building blocks for an iterative approach towards oligomers of the Streptococcus pneumoniae type 1 zwitterionic capsular polysaccharide repeating unit
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Zwitterionic capsular polysaccharide extracts, 8 kDa in mass, from Streptococcus pneumoniae type 1 (Spt1) have shown unique T-cell activating properties. Oligomers of the trisaccharide repeating unit of the Spt1 capsular polysaccharide [3)-4-NH2-α-d-QuipNAc-(14)-α-d-GalpA-(13)-α-d-GalpA-(1-]n of defined length are needed to further investigate this response. An approach towards iteratively extendable trisaccharide building blocks of the zwitterionic capsular polysaccharides of Spt1 is described. Key elements include the comparison of pre-glycosylation oxidation and post-glycosylation oxidation approaches using thioglycoside donors to the target trisaccharide, the optimisation of the post-glycosylation oxidation approach, and the conversion of the trisaccharide to building blocks tailored for iterative glycosylation. The construction and evaluation of stereotunable 2-N-3-O-oxazolidinone donors for the common bacterial 2-acetamido-4-amino-2,4,6-trideoxy-α-d-galactopyranoside motif is also described, as is a key intermediate for their efficient synthesis.
- Ní Cheallaigh, Aisling,Oscarson, Stefan
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p. 940 - 960
(2016/11/17)
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- 'Naked' and hydrated conformers of the conserved core pentasaccharide of N-linked glycoproteins and its building blocks
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N-glycosylation of eukaryotic proteins is widespread and vital to survival. The pentasaccharide unit -Man3GlcNAc2- lies at the protein-junction core of all oligosaccharides attached to asparagine side chains during this process. Although its absolute conservation implies an indispensable role, associated perhaps with its structure, its unbiased conformation and the potential modulating role of solvation are unknown; both have now been explored through a combination of synthesis, laser spectroscopy, and computation. The proximal -GlcNAc-GlcNAc- unit acts as a rigid rod, while the central, and unusual, -Man-β-1,4-GlcNAc- linkage is more flexible and is modulated by the distal Man-α-1,3- and Man-α-1,6- branching units. Solvation stiffens the 'rod' but leaves the distal residues flexible, through a β-Man pivot, ensuring anchored projection from the protein shell while allowing flexible interaction of the distal portion of N-glycosylation with bulk water and biomolecular assemblies.
- Barry, Conor S.,Cocinero, Emilio J.,Carcabal, Pierre,Gamblin, David P.,Stanca-Kaposta, E. Cristina,Remmert, Sarah M.,Fernandez-Alonso, Maria C.,Rudic, Svemir,Simons, John P.,Davis, Benjamin G.
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supporting information
p. 16895 - 16903
(2013/12/04)
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- Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies
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By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using 1H saturation transfer difference (STD) effects and transferred 1H,1H-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides β-d-Galp-(1→4) -β-d-GlcpNAc-OMe and β-d-GlcpNAc-(1→4)-β-d-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/π-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N′-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on 1H NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process. The Royal Society of Chemistry 2012.
- Landstroem, Jens,Bergstroem, Maria,Hamark, Christoffer,Ohlson, Sten,Widmalm, Goeran
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supporting information; experimental part
p. 3019 - 3032
(2012/05/07)
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- Chemoenzymatic synthesis of α2-3-sialylated carbohydrate epitopes
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Sialic acids are common terminal carbohydrates on cell surface. Together with internal carbohydrate structures, they play important roles in many physiological and pathological processes. In order to obtain α2-3-sialylated oligosaccharides, a highly efficient one-pot three-enzyme synthetic approach was applied. The P. multocida-α2-3-sialyltransferase (PmST1) involved in the synthesis was a multifunctional enzyme with extremely flexible donor and acceptor substrate specificities. Sialyltransferase acceptors, including type 1 structure (Galβ1-3GlcNAcβProN 3), type 2 structures (Galβ1-4GlcNAcβProN3 and 6-sulfo-Galβ1-4GlcNAcβProN3), type 4 structure (Galβ1-3GalNAcβProN3), type 3 or core 1 structure (Galβ1-3GalNAcαProN3) and human milk oligoscaccharide or lipooligosaccharide lacto-N-tetraose (LNT) (Galβ1-3GlcNAcβ1- 3Galβ1-4GlcβProN3), were chemically synthesized. They were then used in one-pot three-enzyme reactions with sialic acid precursor ManNAc or ManNGc, to synthesize a library of naturally occurring α2-3-linked sialosides with different internal sugar structures. The sialylated oligosaccharides obtained are valuable probes for their biological studies.
- Huang, Shengshu,Yu, Hai,Chen, Xi
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experimental part
p. 117 - 128
(2011/12/16)
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- Design and synthesis of novel cell wall inhibitors of Mycobacterium tuberculosis GlmM and GlmU
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GlmM and GlmU are key enzymes in the biosynthesis of UDP-N-acetyl-D- glucosamine (UDP-GlcNAc), an essential precursor of peptidoglycan and the rhamnose-GlcNAc linker region in the mycobacterial cell wall. These enzymes are involved in the conversion of two important precursors of UDP-GlcNAc, glucosamine-6-phosphate (GlcN-6-P) and glucosamine-1-phosphate (GlcN-1-P). GlmM converts GlcN-6-P to GlcN-1-P, GlmU is a bifunctional enzyme, whereby GlmU converts GlcN-1-P to GlcNAc-1-P and then catalyzes the formation of UDP-GlcNAc from GlcNAc-1-P and uridine triphosphate. In the present study, methyl 2-amino-2-deoxyl-α-D-glucopyranoside 6-phosphate (1α), methyl 2-amino-2- deoxyl-β-D-glucopyranoside 6-phosphate (1β), two analogs of GlcN-6-P, were synthesized as GlmM inhibitors; 2-azido-2-deoxy-α-D- glucopyranosyl phosphate (2) and 2-amino-2,3-dideoxy-3-fluoro-α- Dglucopyranosyl phosphate (3), analogs of GlcN-1-P, were synthesized firstly as GlmU inhibitors. Compounds 1α, 1β, 2, and 3 as possible inhibitors of mycobacterial GlmM and GlmU are reported herein. Compound 3 showed promising inhibitory activities against GlmU, whereas 1α, 1β and 2 were inactive against GlmM and GlmU even at high concentrations.
- Li, Yongmeng,Zhou, Yan,Mac, Yufang,Li, Xuebing
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scheme or table
p. 1714 - 1720
(2011/12/02)
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- Toward fully synthetic homogeneous β -human Follicle-Stimulating hormone (β -hFSH) with a biantennary N-linked dodecasaccharide. synthesis of β -hFSH with chitobiose units at the natural linkage sites
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A highly convergent synthesis of the sialic acid-rich biantennary N-linked glycan found in human glycoprotein hormones and its use in the synthesis of a fragment derived from the β -domain of human Follicle-Stimulating Hormone (hFSH) are described. The synthesis highlights the use of the Sinay radical glycosidation protocol for the simultaneous installation of both biantennary side-chains of the dodecasaccharide as well as the use of glycal chemistry to construct the tetrasaccharide core in an efficient manner. The synthetic glycan was used to prepare the glycosylated 20-27aa domain of the β -subunit of hFSH under a Lansbury aspartylation protocol. The proposed strategy for incorporating the prepared N-linked dodecasaccharide-containing 20-27aa domain into β -hFSH subunit was validated in the context of a model system, providing protected β -hFSH subunit functionalized with chitobiose at positions 7 and24.
- Nagorny, Pavel,Fasching, Bernhard,Li, Xuechen,Chen, Gong,Aussedat, Baptiste,Danishefsky, Samuel J.
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supporting information; experimental part
p. 5792 - 5799
(2009/09/24)
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- Sweets for catalysis - Facile optimisation of carbohydrate-based bis(oxazoline) ligands
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A new type of carbohydrate-based bis(oxazoline) ligands was prepared from inexpensive D-glucosamine and tested in asymmetric cyclopropanation reactions. For optimisation, modified ligands with 3-O substituents of varying size and electronic properties were prepared as well as a 3-OH unprotected and a perpivaloylated derivative. All new ligands were tested in asymmetric cyclopropanation, revealing a strong dependence of enantioselectivity on steric demand and electronic properties of the 3-O residue. Also, a significant influence of the pyranose conformation, which is determined by the presence or absence of the cyclic acetal group, was observed. Thus, it was easily possible to tune the new carbohydrate bis(oxazoline) ligands to a given reaction.
- Minuth, Tobias,Irmak, Mustafa,Groschner, Annika,Lehnert, Tobias,Boysen, Mike M. K.
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experimental part
p. 997 - 1008
(2009/07/19)
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- A General and efficient route to 3-O-Modified carbohydrate bis(oxazoline) ligands
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An efficient route to derivatives of carbohydrate-based bis(oxazoline) ligands with 3-O substituents of varying steric demand is described. The synthesis of the new ligands proceeds via a thioglucoside key intermediate, the double cyclisation reaction to
- Minuth, Tobias,Boysen, Mike M. K.
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scheme or table
p. 1483 - 1486
(2009/04/07)
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- Synthesis of oligosaccharides corresponding to the polysaccharides of Lactobacillus and Thermophilus strains
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Synthesis of a branched trisaccharide and a tetrasaccharide repeating units corresponding to the polysaccharides of Lactobacillus spp. G-77 and Thermus thermophilus Samu-SA1 as their methyl glycosides has been achieved in excellent yield. Most of the glycosyl linkages are 1,2-cis in these oligosaccharide fragments. Georg Thieme Verlag Stuttgart.
- Mandal, Pintu Kumar,Misra, Anup Kumar
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p. 2660 - 2666
(2008/03/14)
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- Synthesis of deoxygenated disaccharide precursors for modified lipid II synthesis
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The synthesis of novel deoxygenated disaccharide precursors for modified lipid II synthesis is described. The 3- and 4-deoxy-GlcNAc donors were obtained, respectively, by radical reduction of the iodo derivative by TBTH/AIBN and hydrogen reduction of the
- Sun, De-Qun,Busson, Roger,Herdewijn, Piet
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p. 5158 - 5166
(2007/10/03)
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- Synthesis of analogues of calicheamicin and neocarzinostatin chromophore
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The work presents a synthetic route to the CD ring of calicheamicin and in the case of neocarzinostatin an approach to a functionalised cyclopentane-1,3-diol containing the naturally occurring naphthoate and a glucosamine motif. In the case of the NCS derivative some biological activity (cytotoxicity) was observed.
- Cirla, Alessandra,McHale, Angela R.,Mann, John
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p. 4019 - 4029
(2007/10/03)
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- Synthesis of the trisaccharide repeating unit of the O-antigen related to the enterohemorrhagic Escherichia coli type O26:H
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L-Fucose was converted to the 2-azido-2-deoxy-L-fucose derivative, which together with the monosaccharide synthons prepared from L-rhamnose and D-glucosamine hydrochloride were utilized for the synthesis of the p-ethoxyphenyl glycoside of the trisaccharid
- Sarkar, Kakali,Mukherjee, Indrani,Roy, Nirmolendu
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- Efficient synthesis of lactosaminylated core-2 O-glycans
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A series of lactosaminylated oligosaccharides found in mucin type O-glycans was synthesized using a generalized block strategy. The synthesis involved the addition of a protected lactosamine donor to a partially protected T-disaccharide derivative. The nonreducing galactose residues of the deblocked oligosaccharide products could be removed by β-galactosidase from jack bean to produce the corresponding GlcNAc terminated compounds. A series of tri- to hexasaccharides was thus efficiently produced.
- Misra, Anup Kumar,Fukuda, Minoru,Hindsgaul, Ole
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p. 2667 - 2669
(2007/10/03)
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- New effective synthesis of (N-acetyl- and N-stearoyl-2-amino-2-deoxy-β-D-glucopyranosyl)-(1→4)N-acetyln or-muramoyl-L-2-aminobutanoyl-D-isoglutamine, analogs of GMDP with immunopotentiating activity
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Ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (5), prepared by benzylation of ethyl 2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (4), was transformed by reaction with bromine into 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-β-
- Ledvina, Miroslav,Zyka, Daniel,Jezek, Jan,Trnka, Tomas,Saman, David
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p. 577 - 589
(2007/10/03)
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- Application of β-1,4-galactosyltransferase in the synthesis of complex branched-chain oligosaccharide mimics of fragments of the capsular polysaccharide of Streptococcus pneumoniae type 14
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The chemoenzymic synthesis is described of β-D-Galp-(1→4)-β-D-Glcp-(1→6)-[β-D-Galp-(1→4)]- β-D-GlcpNAc-(1→O[CH2] 3O→4)-β-D-Glcp-(1→OCH2CH=CH2) 32 and β-D-Galp-(1→4)-β-D-GlcpNAc-(1→ O[CH2] 3O→4)-β-D-Glcp-(1→6)-[β-D-Galp-(1→4)]- β-D-GlcpNAc-(1→O[CH2] 3O→4)-β-D-Glcp-(1→OCH2-CH=CH2) 33, representing hexa- and octasaccharide mimics of fragments of the Streptococcus pneumoniae type 14 polysaccharide. In a chemical approach the intermediate linear oligosaccharide mimics 30 and 31 were synthesized, wherein both terminal and non-terminal N-acetyl-β-D-glucosamine residues were not yet galactosylated. The alkyl-bridged derivatives were found to be good acceptor substrates for bovine milk β-1,4-galactosyltransferase. Reaction of the anomeric allyl functions with cysteamine under UV-irradiation gave the corresponding 3-(2-aminoethylthio)propyI glycosides 34 and 35, suitable for further coupling of the oligosaccharide mimics to protein carriers.
- Niggemann, Jutta,Kamerling, Johannis P.,Vliegenthart, Johannes F. G.
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p. 3011 - 3020
(2007/10/03)
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- Synthesis of β-D-mannosides from β-D-glucosides via an intramolecular SN2 reaction at C-2
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The selective synthesis of β-D-mannosides was achieved by first synthesizing β-D-glucosides that carry an N-phenylcarbamoyl protecting group at O-3. These derivatives were transformed into the corresponding β-D-mannosides by intramolecular nucleophilic su
- Gunther,Kunz
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p. 217 - 241
(2007/10/02)
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- Improved Synthesis of α-L-Fuc(1->4)-β-D-GlcNAc and α-L-Fuc(1->6)-β-D-GlcNAc Building Blocks: A Convergent Strategy Employing 4-O->6-O Acetyl Migration; NOE Data of the Protected α-1,4-Linked Disaccharide
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The synthesis of the two ethylthio disaccharide building blocks 10 and 17 was achieved by coupling of fucosyl bromide 9 with the acceptor alcohols 6 and 7 under in situ anomerization conditions.The selectively protected 2-deoxy-2-phthalimidoglucose derivative 7 was derived from 6 by utilizing an optimized acetyl migration reaction.The ethylthio function in disaccharides 10 and 17 was activated with bromine, and excess bromine was removed with cyclohexene.The sensitive 1,6-linkage in the disaccharide 10 proved to be stable under these activating conditions.The disaccharide bromides 11 and 18 were treated with methanol to afford after deblocking the methyl glycosides 16 and 23.Homonuclear 1H-NOE data were obtained for the protected 1,4-linked disaccharide 17 suggesting that its preferred solution conformation is rather similar to the solution conformation of the deblocked disaccharide 23 in aqueous solution as known from literature data.Key Words: Oligosaccharide synthesis / Thioglycosides / Acetyl migration / Glycosidic linkage conformation / Carbohydrates
- Peters, Thomas,Weimar, Thomas
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p. 237 - 242
(2007/10/02)
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