- Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation
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The straightforward preparation of glycosyl neoconjugates by oxime (or hydrazone) bond formation represents a key bioorthogonal tool in chemical biology. However, when this strategy is employed by reacting the reducing end of the glycan moiety, the configuration and the stereochemical information is lost due to partial (or complete) opening of the glycan cyclic hemiacetal and the formation of the corresponding opened tautomers. We have completed the synthesis of a library of glycosyl aldehydes to be used as scaffold for the synthesis of neoglycoconjugates via oxime bond formation. These glycosyl aldehydes constitute a simple and accessible alternative to avoid loss of chiral information when conjugating, by oxime (or hydrazone) bonds, the aldehyde functionality present at the reducing end of natural carbohydrates.
- Reina, José J.,Rioboo, Alicia,Montenegro, Javier
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p. 831 - 845
(2018/01/11)
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- Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates
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Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.
- Petrov, Rostislav A.,Maklakova, Svetlana Yu.,Ivanenkov, Yan A.,Petrov, Stanislav A.,Sergeeva, Olga V.,Yamansarov, Emil Yu.,Saltykova, Irina V.,Kireev, Igor I.,Alieva, Irina B.,Deyneka, Ekaterina V.,Sofronova, Alina A.,Aladinskaia, Anastasiia V.,Trofimenko, Alexandre V.,Yamidanov, Renat S.,Kovalev, Sergey V.,Kotelianski, Victor E.,Zatsepin, Timofey S.,Beloglazkina, Elena K.,Majouga, Alexander G.
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p. 382 - 387
(2017/12/26)
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- Synthesis and biological evaluation of novel doxorubicin-containing ASGP-R-targeted drug-conjugates
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Asialoglycoprotein receptor (ASGP-R) belongs to a wide family of C-type lectins and it is currently regarded as an attractive protein in the field of targeted drug delivery (TDD). It is abundantly expressed in hepatocytes and can be found predominantly on the sinusoidal surface especially of HepG2 cells. Therefore, ASGP-R can be used for the TDD of anticancer therapeutics against HCC and molecular diagnostic tools. To date, a variety of mono- and multivalent selective ASGP-R ligands have been discovered. Although many of these compounds have demonstrated a relatively high binding affinity towards the target, the reported synthetic schemes are not handled, complicated and include many non-trivial steps. In the current study, we describe a convenient and versatile synthetic approach to novel monovalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose fragment as an ASGP-R-recognition “core-head” and well-known nonselective cytostatic – Doxorubicin (Dox). This is the first example of the direct conjugation of a drug molecule to the ASGP-targeted warhead by a really convenient manner via a simple linker sequence. The performed MTS-based biological evaluation in HepG2 cells revealed the novel conjugates as having anticancer activity. Confocal microscopy showed that the molecules readily penetrated HepG2 membrane and were mainly localized within the cytoplasm instead of the nucleus. Per contra, Dox under the same conditions demonstrated good anticancer activity and was predominantly concentrated in the nucleus. Therefore, we speculate that the amide “trigger” that we have used in this study for linker attachment is a sufficiently stable inside the cells to be enzymatically or spontaneously degraded. As a consequence, we did not observe the release of the drug. Ligands containing triggers that are more liable towards endogenous hydrolysis within the tissue of targeting are strongly required.
- Ivanenkov, Yan A.,Majouga, Alexander G.,Petrov, Rostislav A.,Petrov, Stanislav A.,Kovalev, Sergey V.,Maklakova, Svetlana Yu.,Yamansarov, Emil Yu.,Saltykova, Irina V.,Deyneka, Ekaterina V.,Filkov, Gleb I.,Kotelianski, Victor E.,Zatsepin, Timofey S.,Beloglazkina, Elena K.
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p. 503 - 508
(2018/01/02)
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- Exploring the Structural Space of the Galectin-1–Ligand Interaction
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Galectin-1 is a tumor-associated protein recognizing the Galβ1-4GlcNAc motif of cell-surface glycoconjugates. Herein, we report the stepwise expansion of a multifunctional natural scaffold based on N-acetyllactosamine (LacNAc). We obtained a LacNAc mimeti
- Bertleff-Zieschang, Nadja,Bechold, Julian,Grimm, Clemens,Reutlinger, Michael,Schneider, Petra,Schneider, Gisbert,Seibel, Jürgen
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p. 1477 - 1481
(2017/08/10)
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- Why Is Direct Glycosylation with N-Acetylglucosamine Donors Such a Poor Reaction and What Can Be Done about It?
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The monosaccharide N-acetyl-d-glucosamine (GlcNAc) is an abundant building block in naturally occurring oligosaccharides, but its incorporation by chemical glycosylation is challenging since direct reactions are low yielding. This issue, generally agreed upon to be caused by an intermediate 1,2-oxazoline, is often bypassed by introducing extra synthetic steps to avoid the presence of the NHAc functional group during glycosylation. The present paper describes new fundamental mechanistic insights into the inherent challenges of performing direct glycosylation with GlcNAc. These results show that controlling the balance of oxazoline formation and glycosylation is key to achieving acceptable chemical yields. By applying this line of reasoning to direct glycosylation with a traditional thioglycoside donor of GlcNAc, which otherwise affords poor glycosylation yields, one may obtain useful glycosylation results.
- Marqvorsen, Mikkel H. S.,Pedersen, Martin J.,Rasmussen, Michelle R.,Kristensen, Steffan K.,Dahl-Lassen, Rasmus,Jensen, Henrik H.
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p. 143 - 156
(2017/04/26)
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- Structurally diverse disaccharide analogs of antifreeze glycoproteins and their ability to inhibit ice recrystallization
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The β-D-galactosyl-(1,3)-α-N-acetyl-D-galactosamine disaccharide is present in antifreeze glycoproteins (AFGPs). Analogs of this disaccharide including the β-linked (1,3)-, (1,4)-, and (1,6)-galactosyl-N-acetyl galactosamine and the β-(1,3)-galactosyl-galactoside were synthesized and evaluated for ice recrystallization inhibition (IRI) activity. The results from this study demonstrate that the b-linked-(1,4) disaccharide exhibits more potent IRI activity than the native b-linked-(1,3) disaccharide. The C2 N-acetyl group of the disaccharide does not affect IRI activity but in monosaccharides, the presence of the C2 N-acetyl group decreases IRI activity. The current study will facilitate the design of potent small-molecule ice recrystallization inhibitors.
- Balcerzak, Anna K.,Ferreira, Sandra S.,Trant, John F.,Ben, Robert N.
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supporting information; experimental part
p. 1719 - 1721
(2012/04/04)
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- Stereoselective dihydroxylation reaction of alkenyl β- D -hexopyranosides: A methodology for the synthesis of glycosylglycerol derivatives and 1-O-Acyl-3-O-β- D -glycosyl-sn-glycerol analogues
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A variety of new glycosylglycerol derivatives have been prepared by stereoselective dihydroxylation of a range of alkenyl β-D-hexopyanosides under Donohoe's conditions. We have studied the relationship between the diastereoisomeric excess and the structural features of the precursor (sugar and alkenyl moieties). The stereochemical yields demonstrated that the presence of a hydrogen-bond donor group (OH, NHAc) at the 2-position of the sugar moiety is required to obtain high levels of stereofacial discrimination. New 1-O-acyl-3-O-β-D-glycosyl-sn-glycerol analogues were obtained by functionalisation of the primary hydroxy group with a fatty acid. Preliminary cytotoxic activity assays of both glycosylglycerol and glycoglycerolipid analogues are also presented. An efficient asymmetric dihydroxylation reaction of alkenyl β-D-hexopyranoside derivatives is described. New glycosylglycerol and glycoglycerolipid analogues have been synthesised by this methodology. Preliminary cytotoxic activity assays are presented. Copyright
- Vega-Perez, Jose M.,Palo-Nieto, Carlos,Perinan, Ignacio,Vega-Holm, Margarita,Calderon-Montano, Jose M.,Lopez-Lazaro, Miguel,Iglesias-Guerra, Fernando
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experimental part
p. 1237 - 1252
(2012/04/10)
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- Synthesis of a mannose-bearing disaccharide with a thiol spacer at the reducing end
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The synthesis of a mannose-bearing disaccharide containing a thiol spacer at the reducing end was carried out to provide a tethered sugar suitable for attaching to gold nanoparticles. An array of such sugars is designed to mimic carbohydrates involved in cell-surface interactions. The molecule was constructed via Schmidt glycosylation of an appropriately protected glycosyl donor and an acceptor, followed by removal of protective groups and reductive amination to introduce a protected thiol spacer at the reducing end of the glycan. A new finding that the anomeric reductive amination is capable of concomitantly removing a neighboring N-acetyl group was also observed. Subsequent removal of the thiol protective group and purification of the product gave the target disaccharide in a satisfactory yield.
- Wang, Chao,Baker, David C.
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experimental part
p. 295 - 300
(2012/05/20)
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- Green glycosylation promoted by reusable biomass carbonaceous solid acid: An easy access to β-stereoselective terpene galactosides
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An efficient green protocol has been developed for the atom economic glycosylation of unprotected, unactivated glycosyl donors and glycosylation of glycosyl trichloroacetimidates with the aid of reusable eco-friendly biomass carbonaceous solid acid as catalyst. The Royal Society of Chemistry.
- Gorityala, Bala Kishan,Ma, Jimei,Pasunooti, Kalyan Kumar,Cai, Shuting,Liu, Xue-Wei
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supporting information; experimental part
p. 573 - 577
(2011/05/06)
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- Olefin cross-metathesis on proteins: Investigation of allylic chalcogen effects and guiding principles in metathesis partner selection
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Olefin metathesis has recently emerged as a viable reaction for chemical protein modification. The scope and limitations of olefin metathesis in bioconjugation, however, remain unclear. Herein we report an assessment of various factors that contribute to productive cross-metathesis on protein substrates. Sterics, substrate scope, and linker selection are all considered. It was discovered during this investigation that allyl chalcogenides generally enhance the rate of alkene metathesis reactions. Allyl selenides were found to be exceptionally reactive olefin metathesis substrates, enabling a broad range of protein modifications not previously possible. The principles considered in this report are important not only for expanding the repertoire of bioconjugation but also for the application of olefin metathesis in general synthetic endeavors.
- Lin, Yuya A.,Chalker, Justin M.,Davis, Benjamin G.
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supporting information; experimental part
p. 16805 - 16811
(2011/02/17)
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- Green glycosylation using ionic liquid to prepare alkyl glycosides for studying carbohydrate-protein interactions by SPR
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Several simple glycosides of d-glucose (Glc) and N-acetyl-d-galactosamine (GalNAc) were prepared in a single step glycosylation reaction using unprotected and unactivated sugar donors. The resulting GalNAc glycoside, containing a bifunctional linker, was used to immobilize this glycoconjugate to a self assembled monolayer on a gold biosensor chip. Surface plasmon resonance (SPR) experiments demonstrated that this immobilized glycoconjugate bound to GalNAc specific lectin, Viscum album agglutinin.
- Javier Munoz,Andre, Sabine,Gabius, Hans-Joachin,Sinisterra, Jose V.,Hernaiz, Maria J.,Linhardt, Robert J.
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experimental part
p. 373 - 379
(2010/04/22)
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- Protecting group free glycosidations using p-toluenesulfonohydrazide donors
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(Figure Presented) N-Glycopyranosylsulfonohydrazides are introduced as glycosyl donors for protecting group free synthesis of O-glycosides, glycosyl azides, and oxazolines. Mono- and disaccharides containing a reducing terminal N-acelylglucosamine residue were condensed with p-toluenesulfonylhydrazide to give the desired β-D-pyranose donors. These donors can be activated with NBS and then glycosidated with the desired alcohol or transformed to the oxazoline or glycosyl azide.
- Gudmundsdottir, Anna V.,Nitz, Mark
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supporting information; scheme or table
p. 3461 - 3463
(2009/04/16)
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- The stereochemical dependence of unimolecular dissociation of monosaccharide-glycolaldehyde anions in the gas phase: A basis for assignment of the stereochemistry and anomeric configuration of monosaccharides in oligosaccharides by mass spectrometry via a key discriminatory product ion of disaccharide fragmentation, m/z 221
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Mass spectrometry of hexose-containing disaccharides often yields product ions of m/z 221 in the negative ion mode. Using a Paul trap, isolation and collision-induced dissociation of the m/z 221 anions yielded mass spectra that easily differentiated their stereochemistry and anomeric configuration, for all 16 stereochemical variants. The ions were shown to be glycopyranosyl- glycolaldehydes through chemical synthesis of their standards. The stereochemistry dramatically affected fragmentation which was dependent on four relative stereochemical arrangements: (1) the relationship between the hydroxyl group at position 2 and the anomeric configuration, (2) a cis relationship of the anomeric position and positions 2 and 3 (1,2,3-cis), (3) a 1,2 trans-2,3 cis relationship, and (4) the relationship between the hydroxyl group at position 4 and the anomeric configuration. After labeling the reducing carbonyl oxygen of a series of disaccharides with 18O to mass-discriminate between their monosaccharide components, it was demonstrated that m/z 221 anions are comprised of an intact nonreducing sugar glycosidically linked to a 2-carbon aglycon derived from the reducing sugar, irrespective of the linkage position between monosaccharides. This enabled the location of the intact sugar to be assigned to the nonreducing side of a glycosidic linkage. Detailed studies of experimental factors necessary for reproducibility demonstrated that the unique mass spectrum for each m/z 221 anion could be obtained from month-to-month through the use of an internal energy-input calibrant ion that ensured reproducible energy deposition into the ions. The counterparts to these ions for the 2-acetamido-2-deoxyhexoses were m/z 262 anions, and the anomeric configuration and stereochemistry of these anions could also be reproducibly discriminated for N-acetylglucosamine and N-acetylgalactosamine. The fragmentation patterns of m/z 221 anions provide a firm reproducible basis for assignment of sugar stereochemistries in the gas phase.
- Fang, Tammy T.,Bendiak, Brad
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p. 9721 - 9736
(2008/03/13)
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- OLIGOSACCHARIDE BIOSYNTHESIS INHIBITORS
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This invention provides a method for inhibiting oligosaccharide biosynthesis in vivo and in vitro comprising the steps of administering at least one monosaccharide derivative, wherein the hydroxyl group which is the glycosyl acceptor (i.e. the active hydr
- -
-
Page/Page column 24; 28-29
(2010/11/28)
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- Chemo-enzymatic synthesis of allyl penta-N-acetyl-chitopentaose
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Cell density cultivation of recombinant Escherichia coli strains harboring the nodC gene (encoding chitooligosaccharide synthase) from Azorhizobium caulinodans has been previously described as a practical method for the preparation of gram-scale quantities of penta-N-acetyl-chitopentaose. We have now extended this method to the production of allylated derivative of penta-N-acetyl-chitopentaose by using allyl 2-acetamido-2-deoxy-β-d- glucopyranoside (2) as the initial acceptor for the synthesis of target pentaoside in vivo.
- Huang, Gang-Liang,Zhang, Da-Wei,Zhao, Hong-Juan,Zhang, Hou-Cheng,Wang, Peng-George
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p. 2042 - 2043
(2007/10/03)
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- Chemo-enzymatic synthesis of 1,4-oxazepanyl sugar as potent inhibitor of chitinase
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N-Acetyl glucosamine 1 is selectively converted into 2 without protection of the other hydroxyl groups by allylation of the anomeric alkoxide in N,N-dimethylformamide containing lithium bromide. We use cell density cultures to produce the allylated derivative of penta-N-acetyl-chitopentaose by using 2 as the initial acceptor for the synthesis of 3 in vivo. Upon periodate oxidation, 3 is transferred to 4. Compound 4 is quickly subjected to sodium borohydride reduction and NH3 amination, which afforded the target compound 5. In 5-binding chitinase assay, it indicates that the chitinase is obviously inactivated by 5 with IC50 = 4.7 μmol/L.
- Huang, Gang-Liang,Zhang, Da-Wei,Zhao, Hong-Juan,Zhang, Hou-Cheng,Wang, Peng-George
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p. 2446 - 2449
(2007/10/03)
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- Facile approach to 2-acetamido-2-deoxy-β-D-glucopyranosides via a furanosyl oxazoline
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(Chemical Equation Presented) A concise and convenient route that may be easily scaled is reported for the preparation of unprotected β-glucopyranosides of N-acetyl-D-glucosamine. Reaction of a wide variety of alcohols with a reactive, readily prepared furanosyl oxazoline under acidic conditions affords the corresponding β-D-glucopyranosides in good to high yields. Primary alcohols gave only β-D-glucopyranosides. A mechanism is proposed for this transformation.
- Cai, Ye,Ling, Chang-Chun,Bundle, David R.
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p. 4021 - 4024
(2007/10/03)
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- Design of N-acetyl-6-sulfo-β-D-glucosaminide-based inhibitors of influenza virus sialidase
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Biological activity of N-acetyl-6-sulfo-β-D-glucosaminides (6-sulfo-GlcNAc 1) having a structural homology to N-acetylneuraminic acid (Neu5Ac 2) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en 3) was examined in terms of inhibitory activity against influenza virus sialidase (influenza, A/Memphis/1/71 H3N2). pNP 6-Sulfo-GlcNAc 1a was proved to show substantial activity to inhibit the virus sialidase (IC50=2.8 mM), though p-nitrophenyl (pNP) GlcNAc without 6-sulfo group and pNP 6-sulfo-GlcNH3+ 1b without 2-NHAc showed little activity (IC50 >50 mM). The activity was enhanced nearly 100-fold when the pNP group of 1a was converted to p-acetamidophenyl one 5 (IC50=30 μM) or replaced with 1-naphthyl 6 (IC50=10 μM) or n-propyl one 8 (IC50=11 μM).
- Sasaki, Kenji,Nishida, Yoshihiro,Kambara, Mikie,Uzawa, Hirotaka,Takahashi, Tadanobu,Suzuki, Takashi,Suzuki, Yasuo,Kobayashi, Kazukiyo
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p. 1367 - 1375
(2007/10/03)
-
- Synthesis and biological activities of lipid A analogs possessing β-glycosidic linkage at 1-position
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New lipid A analogs having acidic groups β-glycosidically linked at the 1-position were synthesized in order to investigate the structural requirement for immunostimulating and endotoxic activity of lipid A. The β-(phosphonoxy)ethyl (PE) and carboxymethyl (CM) analogs of Escherichia coli type having six acyl groups and those of the biosynthetic precursor type having four acyl groups were synthesized via a divergent synthetic route. The E. coli type β-(phosphonoxy)-ethyl analog, which was previously reported to be not endotoxic, showed strong immunostimulating activity comparable to the natural-type α-analog. The acidic functional groups are concluded to be essential but their strict spatial arrangement is not required for expression of the biological activity.
- Fukase, Koichi,Ueno, Atsushi,Fukase, Yoshiyuki,Oikawa, Masato,Suda, Yasuo,Kusumoto, Shoichi
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p. 485 - 500
(2007/10/03)
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- Stereoselective synthesis of epoxyalkyl glycoside precursors of glycosyl glycerol analogues from alkenyl glycosides of N-acetyl-D-glucosamine derivatives
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The synthesis of epoxyalkyl glycoside derivatives of N-acetyl-D-glucosamine is described. Epoxidation of the corresponding alkenyl glycosides with m-CPBA took place with different stereoselectivity depending on the nature of the unsaturated system and the protecting groups on the sugar moiety. The configuration of the newly formed stereogenic centres has been confirmed unequivocally by chemical correlation.
- Vega-Perez, Jose M.,Candela, Jose I.,Blanco, Eugenia,Iglesias-Guerra, Fernando
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p. 2471 - 2483
(2007/10/03)
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- A one-step β-selective glycosylation of N-acetyl glucosamine and recombinant chitooligosaccharides
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N-Acetyl glucosamine and chitooligosaccharides are selectively converted into β-glycosides without protection of the other hydroxyl groups by alkylation of the anomeric alkoxides in N,N-dimethylformamide containing lithium bromide. Addition of the lithium salt notably improves the stereoselectivity of the glycosylation of the monomer and the efficiency of the process with higher oligomers.
- Vauzeilles, Boris,Dausse, Bruno,Palmier, Sara,Beau, Jean-Marie
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p. 7567 - 7570
(2007/10/03)
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- Synthesis and conjugation of oligosaccharide fragments related to the immunologically reactive part of the circulating anodic antigen of the parasite Schistosoma mansoni
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The immunoreactive part of the circulating anodic antigen (CAA) from the parasite Schistosoma mansoni is a threonine-linked polysaccharide consisting of →6)-[β-D-GlcpA-(1→3)]-β-D-GalpNAc-(1→ repeating disaccharides. In the framework of an immunochemical p
- Vermeer, Henricus J.,Halkes, Koen M.,Van Kuik, J. Albert,Kamerling, Johannis P.,Vliegenthart, Johannes F.G.
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p. 2249 - 2263
(2007/10/03)
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- Chemical synthesis of N-acetylglucosamine derivatives and their use as glycosyl acceptors by the Mesorhizobium loti chitin oligosaccharide synthase NodC
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Rhizobial bacteria synthesize lipo-chitin oligosaccharide signal molecules (Nod factors) that are essential for the formation of symbiotic organs on the roots of host plants, a process known as nodulation. Biosynthesis of the chitin oligosaccharide moiety
- Kamst, Eric,Zegelaar-Jaarsveld, Korien,Van Der Marel, Gijs A.,Van Boom, Jacques H.,Lugtenberg, Ben J.J.,Spaink, Herman P.
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p. 176 - 189
(2007/10/03)
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- Regiospecific syntheses of N-acetyllactosamine derivatives and application toward a highly practical synthesis of Lewis X trisaccharide
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An efficient methodology for regiospecific glycosylation was developed by using 6-O-tert-butyldiphenylsilyl N-acetylglucosamine derivatives 3 and 5 which bear two free hydroxyl groups as acceptors. The regiospecificity was attributed to the presence of the tert-butyldiphenylsilyl group at the O-6 position of the N-acetylglucosamine derivatives. Glycosylation of suitably protected galactoside donors 10-14 with acceptors 3 and 5 gave only β(1→4) linked disaccharides 15-19 in good yields. Fucosylation of disaccharide 18 led to Lewis X (Lex) trisaccharide 21 in high yield.
- Gan, Zhonghong,Cao, Suoding,Wu, Qingquan,Roy, Rene
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p. 755 - 773
(2007/10/03)
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- Degradation of Derivatives of N-Acetyl-D-glucosamine by Rhodococcus rhodochrous IFO 15564: Substrate Specificity and Its Application to the Synthesis of Allyl α-N-Acetyl-D-glucosaminide
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The substrate specificity was studied for the metabolic degradation of N-acetyl-D-glucosamine (GIcNAc) derivatives by Rhodococcus rhodochrous IFO 15564 which possesses N-acetyl-D-glucosamine deacetylase as a key-step enzyme. This microorganism degraded a wide range of substrates with modified N-acyl groups. The metabolizing activity of this strain became low to the substrates substituted at 1,3,4,6-positions of GlcNAc, and GlcNAc itself was suggested to be metabolized via an open-chain aldehyde form. Based on these results, a simplified procedure for the isolation of allyl α-N-acetyl-D-glucosaminide from an α, β-anomeric mixture was developed by selectively hydrolyzing the β-anomer with Jackbean β-N-acetyl-D-glucosaminidase and subsequently degrading the resulting N-acetyl-D-glucosamine in the reaction mixture with this microorganism.
- Kuboki, Atsuhito,Komiya, Ryosuke,Sekiguchi, Takahiro,Katsuragi, Kenji,Sugai, Takeshi,Ohta, Hiromichi
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p. 1581 - 1585
(2007/10/03)
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- Chemoenzymatic synthesis of an N-acetylneuraminic acid analogue having a carbamoylmethyl group at C-4 as an inhibitor of sialidase from influenza virus
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5,9-Diacetamido-2,6-anhydro-O-4-carbamoylmethyl-3,5,9-trideoxy-d-glycero-d-galacto-non-2-enonic acid (1) was synthesized via a key intermediate 2 through the Neu5Ac aldolase [E.C.4.1.3.3]-catalyzed aldol reaction of 2-acetamido-2,6-dideoxy-6-azido-d-glucose with sodium pyruvate operating under alkaline conditions (pH 10.5) in order to accelerate epimerization C-2 of N-acetyl-d-glucosamine (d-GlcNAc) derivatives. Compound 1 showed inhibitory activity against sialidase. Copyright (C) 1998 Elsevier Science Ltd.
- Ikeda, Kiyoshi,Kimura, Fuyuki,Sano, Kimihiko,Suzuki, Yasuo,Achiwa, Kazuo
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p. 183 - 189
(2007/10/03)
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- Conformational differences between Fuc(α1-3)GlcNAc and its thioglycoside analogue
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NOE measurements and molecular mechanics calculations have been performed to study the conformational behaviour of Fuc(α1-3)GlcNAc and its thioglycoside analogue in solution. Experimental data show that, in contrast with the natural O-disaccharide, which
- Aguilera, Begona,Jimenez-Barbero, Jesus,Fernandez-Mayoralas, Alfonso
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-
- Solid phase synthesis of peptidoglycan monomers for the generation of a combinatorial library
-
Solid phase synthesis of peptidoglycan monomers was conducted by coupling the corresponding lipid-bearing glycocarboxylic acids to resin-bound peptides. The efficiency of coupling reagents was found to be in descending order of HATU > HBTU > PyBOP > EEDQ. There was no obvious difference in coupling yield between conducting the solid phase synthesis on polystyrene resins or on polyethylene glycol grafted polystyrene resins.
- Chan, Tin Yau,Chen, Anna,Allanson, Nigel,Chen, Ru,Liu, Dashan,Sofia, Michael J.
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p. 8097 - 8100
(2007/10/03)
-
- Chemical Synthesis of a Biosynthetic Precursor of Lipid A with a Phosphorylated Tetraacyl Disaccharide Structure
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2,2'-N:3,3'-O-Tetrakis-β(1-6)-D-glucosamine disaccharide 1,4'-bis(phosphate) and its dephospho derivatives were synthesized.The bisphosphate prepared was shown to be identical with a natural biosynthetic precursor of lipid A which corresponds to the lipophilic part of lipopolysaccharide (LPS) in bacterial cell wall.The synthetic bis- and monophosphates exhibited many of typical endotoxic activities of LPS.Consequently, this work established the chemical structure of the biosynthetic precursor of lipid A and elucidated the fundamental structure required for the expression of these activities.
- Imoto, Masahiro,Yoshimura, Hiroyuki,Yamamoto, Michiharu,Shimamoto, Tetsuo,Kusumoto, Shoichi,Shiba, Tetsuo
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p. 2197 - 2204
(2007/10/02)
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- Synthesis of D-galactosamine derivatives and binding studies using isolated rat hepatocytes.
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Derivatives of glycosides of D-galactosamine were prepared in order to study further the binding requirement of the Gal/GalNAc receptor in mammalian hepatocytes. These structures included N-propanoyl, N-benzoyl, and N,N-phthaloyl derivatives of 2-hydroxye
- Wong,Townsend,Lee
-
-
- CHEMICAL SYNTHESIS OF PHOSPHORYLATED TETRAACYL DISACCHARIDE CORRESPONDING TO A BIOSYNTHETIC PRECURSOR OF LIPID A
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A total synthesis of 2,2'-N; 3,3'-O-tetraquis-β(1-6)-D-glucosamine disaccharide 1,4'-diphosphate is described.This is the first confirmation of the fundamental structure of lipid A since the synthetic compound exhibited most of the characteristic biological activities of natural endotoxin.
- Imoto, M.,Yoshimura, H.,Yamamoto, M.,Shimamoto, T.,Kusumoto, S.,Shiba, T.
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p. 2667 - 2670
(2007/10/02)
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