- Amide Cis-trans isomerization in aqueous solutions of methyl N -Formyl- d -glucosaminides and Methyl N -Acetyl- d -glucosaminides: Chemical equilibria and exchange kinetics
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Amide cis-trans isomerization (CTI) in methyl 2-deoxy-2-acylamido-d- glucopyranosides was investigated by 1H and 13C NMR spectroscopy. Singly 13C-labeled methyl 2-deoxy-2-formamido-d- glucopyranoside (MeGlcNFm) anomers provided standard 1H and 13C chemical shifts and 1H-1H and 13C-13C spin-coupling constants for cis and trans amides that are detected readily in aqueous solution. Equipped with this information, doubly 13C-labeled methyl 2-deoxy-2-acetamido-d-glucopyranoside (MeGlcNAc) anomers were investigated, leading to the detection and quantification of cis and trans amides in this biologically important aminosugar. In comparison to MeGlcNFm anomers, the percentage of cis amide in aqueous solutions of MeGlcNAc anomers is small (~23% for MeGlcNFm versus ~1.8% for MeGlcNAc at 42 °C) but nevertheless observable with assistance from 13C-labeling. Temperature studies gave thermodynamic parameters δG°, δH°, and δS° for cis-trans interconversion in MeGlcNFm and MeGlcNAc anomers. Cis/trans equilibria depended on anomeric configuration, with solutions of α-anomers containing less cis amide than those of β-anomers. Confirmation of the presence of cis amide in MeGlcNAc solutions derived from quantitative 13C saturation transfer measurements of CTI rate constants as a function of solution temperature, yielding activation parameters Eact, δG° ?, δH°-, and δS° ? for saccharide CTI. Rate constants for the conversion of trans to cis amide in MeGlcNFm and MeGlcNAc anomers ranged from 0.02 to 3.59 s-1 over 31-85 °C, compared to 0.24-80 s-1 for the conversion of cis to trans amide over the same temperature range. Energies of activation ranged from 16-19 and 19-20 kcal/mol for the cis → trans and trans → cis processes, respectively. Complementary DFT calculations on MeGlcNFm and MeGlcNAc model structures were conducted to evaluate the effects of an acyl side chain and anomeric structure, as well as C2-N2 bond rotation, on CTI energetics. These studies show that aqueous solutions of GlcNAc-containing structures contain measurable amounts of both cis and trans amides, which may influence their biological properties.
- Hu, Xiaosong,Zhang, Wenhui,Carmichael, Ian,Serianni, Anthony S.
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Read Online
- A de Novo-Designed Monomeric, Compact Three-Helix-Bundle Protein on a Carbohydrate Template
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De novo design and chemical synthesis of proteins and of other artificial structures that mimic them is a central strategy for understanding protein folding and for accessing proteins with new functions. We have previously described carbohydrates that act as templates for the assembly of artificial proteins, so-called carboproteins. The hypothesis is that the template preorganizes the secondary structure elements and directs the formation of a tertiary structure, thus achieving structural economy in the combination of peptide, linker, and template. We speculate that the structural information from the template could facilitate protein folding. Here we report the design and synthesis of three-helix-bundle carboproteins on deoxyhexopyranosides. The carboproteins were analyzed by CD, analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and NMR spectroscopy, and this revealed the formation of the first compact and folded monomeric carboprotein, distinctly different from a molten globule. En route to this carboprotein we observed a clear effect originating from the template on protein folding.
- Malik, Leila,Nygaard, Jesper,Cristensen, Niels J.,Madsen, Charlotte S.,R?sner, Heike I.,Kragelund, Birthe B.,Hoiberg-Nielsen, Rasmus,Streicher, Werner W.,Arleth, Lise,Thulstrup, Peter W.,Jensen, Knud J.
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Read Online
- Stoichiometric C6-oxidation of hyaluronic acid by oxoammonium salt TEMPO+Cl- in an aqueous alkaline medium
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This paper reports the selective oxidation of hyaluronic acid (HA) by stoichiometric quantity of 2,2,6,6-tetramethylpiperidine-1-oxoammonium chloride (TEMPO+) in aqueous alkaline medium. High efficiency of the HA oxidation and quantitative yield of carboxy-HA per starting TEMPO+, as well as unusual behavior of the oxidation system generating an oxygen upon alkali-induced oxoammonium chloride decomposition are demonstrated. The scheme for HA oxidation involving both TEMPO+ and oxygen produced upon the TEMPO+Cl- decomposition and/or air oxygen is proposed. For comparison, the data on stoichiometric oxidation of such substrates as dermatan sulfate, water-soluble potato starch, methyl 2-acetamido-2-deoxy-β-d-glucopyranoside and ethanol are presented.
- Ponedel'Kina, Irina Yu,Khaibrakhmanova, Elvira A.,Tyumkina, Tatyana V.,Romadova, Irina V.,Odinokov, Victor N.
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Read Online
- Synthesis and Study of Molecular Assemblies Formed by 4,6-O-(2-Phenylethylidene)-Functionalized d -Glucosamine Derivatives
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Low-molecular-weight gelators are interesting small molecules with potential applications as advanced materials. Carbohydrate-based small molecular gelators are especially useful because they are derived from renewable resources and are more likely to be biocompatible and biodegradable. Various 4,6-benzylidene acetal protected α-methyl 2-d-glucosamine derivatives have been found to be effective low-molecular-weight gelators. To understand the influence of the 4,6-benzylidene acetal functional group toward molecular self-assembly and to obtain effective molecular gelators, we synthesized and analyzed a new series of d-glucosamine derivatives in which the phenyl group of the acetal is replaced by a benzyl group. The homologation of the acetal protection from aromatic to aliphatic functional groups allows us to probe the effect of increasing structural flexibility on molecular self-assembly and gelation. In this study, nine representative amides and nine urea analogs were synthesized, and their gelation properties were analyzed in a series of organic solvents and aqueous solutions. The resulting amide and urea derivatives are versatile organogelators forming gels in toluene, ethanol, isopropanol, ethylene glycol, and aqueous mixtures of organic solvents. More interestingly, the amide analogs are also effective gelators for pump oil and engine oil. NMR spectroscopy at variable temperatures was used to analyze the molecular assemblies and intermolecular forces. The selected gelators with several drug and dye molecules in DMSO and water were studied for their effectiveness of encapsulation and release of these agents.
- Chen, Anji,Adhikari, Surya B.,Mays, Kellie,Wang, Guijun
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Read Online
- O-Acetylated sugars in the gas phase: stability, migration, positional isomers and conformation
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O-Acetylations are functional modifications which can be found on different hydroxyl groups of glycans and which contribute to the fine tuning of their biological activity. Localizing the acetyl modifications is notoriously challenging in glycoanalysis, in particular because of their mobility: loss or migration of the acetyl group may occur through the analytical workflow. Whereas migration conditions in the condensed phase have been rationalized, little is known about the suitability of Mass Spectrometry to retain and resolve the structure of O-acetylated glycan isomers. Here we used the resolving power of infrared ion spectroscopy in combination with ab initio calculations to assess the structure of O-acetylated monosaccharide ions in the gaseous environment of a mass analyzer. N-Acetyl glucosamines were synthetized with an O-acetyl group in positions 3 or 6, respectively. The protonated ions produced by electrospray ionization were observed by mass spectrometry and their vibrational fingerprints were recorded in the 3 μm range by IRMPD spectroscopy (InfraRed Multiple Photon Dissociation). Experimentally, the isomers show distinctive IR fingerprints. Additionally, ab initio calculations confirm the position of the O-acetylation and resolve their gas phase conformation. These findings demonstrate that the position of O-acetyl groups is retained through the transfer from solution to the gas phase, and can be identified by IRMPD spectroscopy.
- Allouche, Abdul-Rahman,Chambert, Stéphane,Compagnon, Isabelle,Gharbi, Amira,Rouillon, Jean,Schindler, Baptiste,Yeni, Oznur
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p. 1016 - 1022
(2022/02/01)
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- Design, physico-chemical characterization andin vitrobiological activity of organogold(iii) glycoconjugates
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To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic gold(iii)-dithiocarbamato glycoconjugates of the type [AuIII(2-Bnpy)(SSC-Inp-GlcN)](PF6) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moie
- Pettenuzzo, Andrea,Vezzù, Keti,Di Paolo, Maria Luisa,Fotopoulou, Eirini,Marchiò, Luciano,Via, Lisa Dalla,Ronconi, Luca
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supporting information
p. 8963 - 8979
(2021/07/02)
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- Synthetic development of sugar amino acid oligomers towards novel podophyllotoxin analogues
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In this work, we have developed an approach for the synthesis of sugar amino acid oligomers based on the glucosamine scaffold. We found that the solid-phase approach was unsuccessful for the preparation of sugar amino acid oligomers and the limitation of
- Bouchard, Megan,Tremblay, Thomas,Paré-Lacroix, Marie-Pier,Gagné-Boulet, Mathieu,Fortin, Sébastien,Giguère, Denis
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- Ultrasonication-Assisted Synthesis of a d-Glucosamine-Based β-CD Inclusion Complex and Its Application as an Aqueous Heterogeneous Organocatalytic System
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For the first time, an inclusion complex has been crafted between a carbohydrate-based molecule and a β-cyclodextrin (CD) hydrophobic cavity for asymmetric catalytic applications. This novel d-glucosamine-based inclusion compound has been synthesized in h
- Rani, Dhiraj,Sethi, Aaftaab,Kaur, Khushwinder,Agarwal, Jyoti
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p. 9548 - 9557
(2020/09/09)
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- Synthesis of glucosamine vinyl ether derivative and its deuterated analog
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The use of calcium carbide (in the presence of H2O) as a source of acetylene in the reaction with methyl 2-amino-4,6-O-benzylidene-2-deoxy-β-d-glucopyranoside under superbasic conditions (KF, KOH, DMSO, 130 °C, 3 h) led to the corresponding vin
- Ledovskaya, M. S.,Rodygin, K. S.,Voronin, V. V.
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p. 1401 - 1404
(2020/09/07)
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- Efficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists
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Carbohydrates are involved in many important pathological processes, such as bacterial and viral infections, by means of carbohydrate-protein interactions. Glycoconjugates with multiple carbohydrates are involved in multivalent interactions, thus increasing their binding strengths to proteins. In this work, we report the efficient synthesis of novel muramic and glucuronic acid glycodendrimers as potential Dengue virus antagonists. Aromatic scaffolds functionalized with a terminal ethynyl groups were coupled to muramic and glucuronic acid azides by click chemistry through optimized synthetic strategies to afford the desired glycodendrimers with high yields. Surface Plasmon Resonance studies have demonstrated that the compounds reported bind efficiently to the Dengue virus envelope protein. Molecular modelling studies were carried out to simulate and explain the binding observed. These studies confirm that efficient chemical synthesis of glycodendrimers can be brought about easily offering a versatile strategy to find new active compounds against Dengue virus.
- García-Oliva, Cecilia,Cabanillas, Alfredo H.,Perona, Almudena,Hoyos, Pilar,Rumbero, ángel,Hernáiz, María J.
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p. 1588 - 1596
(2020/02/05)
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- Methyl glycosides via Fischer glycosylation: translation from batch microwave to continuous flow processing
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Abstract: A continuous flow procedure for the synthesis of methyl glycosides (Fischer glycosylation) of various monosaccharides using a heterogenous catalyst has been developed. In-depth analysis of the isomeric composition was undertaken and high consistency with corresponding results observed under microwave heating was obtained. Even in cases where addition of water was needed to achieve homogeneity—a prerequisite for the flow experiments—no detrimental effect on the conversion was found. The scalability was demonstrated on a model case (mannose) and as part of the target-oriented synthesis of d-glycero-d-manno heptose, both performed on multigram scale.
- Aronow, Jonas,Stanetty, Christian,Baxendale, Ian R.,Mihovilovic, Marko D.
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- Kinetically Controlled Fischer Glycosidation under Flow Conditions: A New Method for Preparing Furanosides
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Kinetically controlled Fischer glycosidation was achieved under flow conditions. β-Hydroxy-substituted sulfonic acid functionalized silica (HO-SAS) was used as an acid catalyst. This reaction directly converted aldohexoses into kinetically favored furanosides to enable the practical synthesis of furanosides. After optimization of the reaction temperature and residence time, glucofuranosides, galactofuranosides, and mannofuranosides were synthesized in good yields.
- Masui, Seiji,Manabe, Yoshiyuki,Hirao, Kohtaro,Shimoyama, Atsushi,Fukuyama, Takahide,Ryu, Ilhyong,Fukase, Koichi
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supporting information
p. 397 - 400
(2019/02/26)
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- Triazole Linked N-Acetylglucosamine Based Gelators for Crude Oil Separation and Dye Removal
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Marine oil-spills have a long-lasting impact on the environment; therefore, it is a major concern in the scientific community to find a solution for remediation. Recently, phase selective organo-gelators emerged as potential materials for removal of oil from water through selective gelation. Herein, we report synthesis of a series of C-6 triazole linked N-acetylglucosamine derivatives, among which three have shown excellent selective gelation of organic solvents, diesel, petrol, and crude oils in water and seawater. We have studied phase selective gelation against different API grade crude oils (from light to heavy), and the gelation was achieved using nontoxic carrier solvent at room temperature in less than 15 min, and gelators were found useful for recovering crude oils. Critical gel concentration (CGC) of crude oil gelators was found to be 2.3-12% (w/v). The variable temperature NMR and FTIR experiments reveal that intermolecular hydrogen bonding was responsible for gel formation. Furthermore, a gelator was utilized for selective dye removal from water.
- Narayana, Chintam,Kumari, Priti,Tiwari, Ghanshyam,Sagar, Ram
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p. 16803 - 16812
(2019/12/27)
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- An innovative and efficient route to the synthesis of metal-based glycoconjugates: proof-of-concept and potential applications
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With a view to developing more efficient strategies to the functionalization of metallodrugs with carbohydrates, we here report on an innovative and efficient synthetic route to generate gold(iii) glycoconjugates in high yields and purity. The method is based on the initial synthesis of the zinc(ii)-dithiocarbamato intermediate [ZnII(SSC-Inp-GlcN)2] (Inp = isonipecotic moiety; GlcN = amino-glucose) followed by the transfer of the glucoseisonipecoticdithiocarbamato ligand to the gold(iii) center via transmetallation reaction between the zinc(ii) intermediate and K[AuIIIBr4] in 1?:?2 stoichiometric ratio, yielding the corresponding glucose-functionalized gold(iii)-dithiocarbamato derivative [AuIIIBr2(SSC-Inp-GlcN)]. No protection/deprotection of the amino-glucose scaffold and no chromatographic purification were needed. The synthetic protocol was optimized for glucose precursors bearing the amino function at either the C2 or the C6 position, and works in the case of both α and β anomers. The application of the synthetic strategy was also successfully extended to other metal ions of biomedical interest, such as gold(i) and platinum(ii), to obtain [AuI(SSC-Inp-GlcN)(PPh3)] and [PtII(SSC-Inp-GlcN)2], respectively. All compounds were fully characterized by elemental analysis, mid- and far-IR, mono- and multidimensional NMR spectroscopy, and, where possible, X-ray crystallography. Results and potential applications are here discussed.
- Pettenuzzo, Andrea,Montagner, Diego,McArdle, Patrick,Ronconi, Luca
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supporting information
p. 10721 - 10736
(2018/08/17)
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- Ring-Opening Reactions of the N-4-Nosyl Hough-Richardson Aziridine with Nitrogen Nucleophiles
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Dinosylated α-d-glucopyranoside was directly transformed into α-d-altropyranosides via in situ formed N-4-nosyl Hough-Richardson aziridine with nitrogen nucleophiles under mild conditions in fair to excellent yields. The scope of the aziridine ring-opening reaction was substantially broadened contrary to the conventional methods introducing solely the azide anion at high temperatures. If necessary, the N-4-nosyl Hough-Richardson aziridine can be isolated by filtration in a very good yield and high purity.
- Ru?il, Tomá?,Trávní?ek, Zdeněk,Canka?, Petr
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p. 723 - 730
(2017/04/26)
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- A versatile carbohydrate based gelator for oil water separation, nanoparticle synthesis and dye removal
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A versatile green gelator suitable for multiple applications is reported. Gelation of organic solvents in a significantly low gelation time (5 s) is achieved. The effect of cooling and sonication on gelation time is investigated. Apart from organic solve
- Narayana, Chintam,Upadhyay, Ravi Kant,Chaturvedi, Raman,Sagar, Ram
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supporting information
p. 2261 - 2267
(2017/03/22)
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- Sugar derived alkamine catalytic imine reduction method
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The invention discloses a method used for catalytic reduction of imine with saccharide-derivatized amino alcohol. According to the method, imine is taken as a substrate. The method comprises following steps: 1) imine and saccharide-derivatized amino alcohol are dissolved in an organic solvent I, wherein molar ratio of imine to saccharide-derivatized amino alcohol ranges from 100:1-20; 2) trichlorosilane with 1.5 to 5 times equivalent weights is added into a solution obtained via step 1) dropwise, an obtained mixture is stirred and reacted for 12 to 36h at a temperature of -20 to 40 DEG C, and a saturated sodium bicarbonate solution is used for quenching; 3) a material obtained via step 2) is extracted with an organic solvent II, and is subjected to column chromatography isolation so as to obtain amine compounds.
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- N-acetylgalactosamine green synthetic method
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The present invention discloses a N-acetylgalactosamine green synthetic method. According to the method, N-acetylglucosamine as a raw material is successively condensed with an alcohol and pivaloyl chloride, and then N-acetylgalactosamine can be obtained
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Paragraph 0037; 0038
(2016/11/28)
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- Synthetic heparin pentasaccharides
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Preparation and use of synthetic monosaccharides, disaccharides, trisaccharides, tetrasaccharides and pentasaccharides useful for the preparation of synthetic heparinoids.
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Page/Page column 36; 37
(2016/02/12)
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- A disaccharide intermediate fragment [...] BA and its synthetic method
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The invention discloses a fondaparinux sodium disaccharide intermediate fragment BA and a synthetic method thereof. The synthetic method is novel in synthesis strategy, available in raw materials, relatively fewer in reaction steps, mild in reaction condi
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Paragraph 0037-0038
(2017/01/31)
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- PRODUCTION METHOD OF ALKYL N-ACETYLGLUCOSAMINIDE
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PROBLEM TO BE SOLVED: To provide a method for obtaining alkyl N-acetylglucosaminide that comprises few content of N-acetyl glucosamine as impurities, conveniently and efficiently with a low cost. SOLUTION: The invention provides a production method of alkyl N-acetylglucosaminide comprising a step of reducing the content of N-acetyl glucosamine by contacting a mixture of alkyl N-acetylglucosaminide and N-acetyl glucosamine with strongly basic anion exchange resin (where, alkyl means an alkyl group of carbon number 1-4). The invention relates to the production method of alkyl N-acetylglucosaminide which is a mixture of alkyl N-acetylglucosaminide and N-acetyl glucosamine obtained by reaction of N-acetyl glucosamine, chitin, or chitin oligosaccharide with alkyl alcohol under the presence of an acid, or transglycosidation of chitin or chitin oligosaccharide using an enzyme with N-acetylhexosaminidase activity in a mixed solution of alkyl alcohol and water. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0034; 0035
(2016/12/01)
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- Chemo-enzymatic approach to access diastereopure α-substituted GlcNAc derivatives
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The formation of diastereopure α-substituted GlcNAc derivatives in a simple and straightforward way is a challenging task. Herein, we report the chemical synthesis of diastereomeric α/β-substituted GlcNAc derivatives under non-anhydrous atmosphere using u
- Wang, Su-Yan,Laborda, Pedro,Lu, Ai-Min,Wang, Meng,Duan, Xu-Chu,Liu, Li,Voglmeir, Josef
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p. 423 - 434
(2017/08/23)
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- Catalytic Depolymerization of Chitin with Retention of N-Acetyl Group
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Chitin, a polymer of N-acetylglucosamine units with β-1,4-glycosidic linkages, is the most abundant marine biomass. Chitin monomers containing N-acetyl groups are useful precursors to various fine chemicals and medicines. However, the selective conversion of robust chitin to N-acetylated monomers currently requires a large excess of acid or a long reaction time, which limits its application. We demonstrate a fast catalytic transformation of chitin to monomers with retention of N-acetyl groups by combining mechanochemistry and homogeneous catalysis. Mechanical-force-assisted depolymerization of chitin with a catalytic amount of H2SO4 gave soluble short-chain oligomers. Subsequent hydrolysis of the ball-milled sample provided N-acetylglucosamine in 53 % yield, and methanolysis afforded 1-O-methyl-N-acetylglucosamine in yields of up to 70 %. Our process can greatly reduce the use of acid compared to the conventional process.
- Yabushita, Mizuho,Kobayashi, Hirokazu,Kuroki, Kyoichi,Ito, Shogo,Fukuoka, Atsushi
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p. 3760 - 3763
(2015/12/08)
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- Nucleophilic Aromatic Substitution (SNAr) as an Approach to Challenging Carbohydrate-Aryl Ethers
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A general and practical route to carbohydrate-aryl ethers by nucleophilic aromatic substitution (SNAr) is reported. Upon treatment with KHMDS, C-O bond formation occurs between carbohydrate alcohols and a diverse range of fluorinated (hetero)ar
- Henderson, Alexander S.,Medina, Sandra,Bower, John F.,Galan, M. Carmen
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p. 4846 - 4849
(2015/10/12)
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- Diaminohexopyranosides as ligands in half-sandwich ruthenium(II), rhodium(III), and iridium(III) complexes
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The syntheses of methyl 2,3-diamino-4,6-O-benzylidene-2,3-dideoxy-α-d-hexopyranosides of glucose, mannose, gulose, and talose and methyl 2-amino-4,6-benzylidene-2,3-dideoxy-3-tosylamido-α-d-glucopyranoside are exhaustively presented, as well as their application as ligands in half-sandwich ruthenium(II), rhodium(III), and iridium(III) complexes. The complex formation occurs highly diastereoselectively, creating a stereogenic metal center. The molecular structures of the ligands and their complexes were investigated by X-ray structure analysis, NMR spectroscopy, polarimetry, and DFT methods. The diamino monosaccharide complexes have been subjected to antitumor activity studies. In vitro tests of a few ruthenium complexes against different cancer cell types showed antiproliferative activities 4-10 times lower than that of cisplatin.
- B?ge, Matthias,Fowelin, Christian,Bednarski, Patrick,Heck, Jürgen
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p. 1507 - 1521
(2015/05/13)
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- D-Glucosamine as a novel chiral auxiliary for the stereoselective synthesis of P-stereogenic phosphine oxides
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D-Glucosamine was successfully employed as a chiral auxiliary for the enantioselective synthesis of phosphine oxides. The influence of the anomeric position was also investigated and revealed the excellent ability of the α-anomer to perform this transform
- D'Onofrio,Copey,Jean-Gérard,Goux-Henry,Pilet,Andrioletti,Framery
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supporting information
p. 9029 - 9034
(2015/09/01)
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- Synthesis of modified Trichinella spiralis disaccharide epitopes and a comparison of their recognition by chemical mapping and saturation transfer difference NMR
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A rat monoclonal antibody 9D4 raised against the cell surface N-glycan of the parasite Trichinella spirallis protects rats against further infection. The terminal disaccharide β-d-Tyvp(1→3)β-d-GalNAcp (2) represents the immunodominant portion of the antig
- Cui, Lina,Ling, Chang-Chun,Sadowska, Joanna,Bundle, David R.
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- Synthesis and characterization of pH responsive D-glucosamine based molecular gelators
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Small molecular gelators are a class of compounds with potential applications for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protect
- Goyal, Navneet,Mangunuru, Hari P.R.,Parikh, Bargav,Shrestha, Sonu,Wang, Guijun
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supporting information
p. 3111 - 3121
(2015/03/03)
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- Synthesis and evaluation of inhibitors of E. coli PgaB, a polysaccharide de-N-acetylase involved in biofilm formation
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Many medically important biofilm forming bacteria produce similar polysaccharide intercellular adhesins (PIA) consisting of partially de-N-acetylated β-(1 → 6)-N-acetylglucosamine polymers (dPNAG). In Escherichia coli, de-N-acetylation of the β-(1 → 6)-N-
- Chibba, Anthony,Poloczek, Joanna,Little, Dustin J.,Howell, P. Lynne,Nitz, Mark
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supporting information; experimental part
p. 7103 - 7107
(2012/10/08)
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- Novel phosphoramidate prodrugs of N-acetyl-(d)-glucosamine with antidegenerative activity on bovine and human cartilage explants
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(d)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis (OA), a chronic and degenerative articular joint disease. In our preceding paper, a series of novel O-6 phosphate N-acetyl (d)-glucosamine prod
- Serpi, Michaela,Bibbo, Rita,Rat, Stephanie,Roberts, Helen,Hughes, Claire,Caterson, Bruce,Alcaraz, María José,Gibert, Anna Torrent,Verson, Carlos Raul Alaez,McGuigan, Christopher
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supporting information; experimental part
p. 4629 - 4639
(2012/07/01)
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- Synthesis and characterization of monosaccharide derivatives and application of sugar-based prolinamides in asymmetric synthesis
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For the first time, the β-anomer of N-acetylglucosamine derivative methyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranoside (9b) was synthesized, isolated, and used in the synthesis of sugar-based primary amine 4b. Sugar-based primary amine 5a, a
- Agarwal, Jyoti,Peddinti, Rama Krishna
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p. 6390 - 6406,17
(2020/09/16)
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- Glucosamine-based primary amines as organocatalysts for the asymmetric aldol reaction
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Glucosamine derivatives have been synthesized starting from commercially available N-acetyl-D-glucosamine/glucosamine hydrochloride and have been employed successfully as efficient organocatalysts for the direct asymmetric aldol reaction between cyclohexa
- Agarwal, Jyoti,Peddinti, Rama Krishna
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scheme or table
p. 3502 - 3505
(2011/06/21)
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- Oligo-Aminosaccharide compound
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An oligo-aminosaccharide compound formed by binding 3 to 6 saccharides, such as 2,6-diamino-2,6-dideoxy-α-(1→4)-D-glucopyranose oligomers, or a salt thereof, which has high affinity to a double-stranded nucleic acid.
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Page/Page column 8
(2011/01/12)
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- Synthesis and characterization of d-glucosamine-derived low molecular weight gelators
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Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many potential applications. Previously, we have found that certain esters and carbamates of 4,6-O-benzylidene-α-d-methyl- glucopyranoside are low molecular weight
- Goyal, Navneet,Cheuk, Sherwin,Wang, Guijun
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supporting information; experimental part
p. 5962 - 5971
(2010/09/18)
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- Accessible sugars as asymmetric olefin epoxidation organocatalysts: Glucosaminide ketones in the synthesis of terminal epoxides
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A systematically varied series of conformationally restricted ketones, readily prepared from N-acetyl-d-glucosamine, were tested against representative olefins as asymmetric epoxidation catalysts showing useful selectivities against terminal olefins and, in particular, typically difficult 2,2-disubstituted terminal olefins.
- Boutureira, Omar,McGouran, Joanna F.,Stafford, Robert L.,Emmerson, Daniel P. G.,Davis, Benjamin G.
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supporting information; experimental part
p. 4285 - 4288
(2009/12/05)
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- Synthesis and conformational analysis of glycomimetic analogs of thiochitobiose
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The synthesis of six analogs of N,N′-diacetylchitobiose is reported, including a novel transglycosylation reaction for the preparation of S-aryl thioglycosides. The conformations of the compounds were studied by a combination of NMR spectroscopy and molec
- Fettke, Anja,Peikow, Dirk,Peter, Martin G.,Kleinpeter, Erich
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supporting information; experimental part
p. 4356 - 4366
(2009/10/09)
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- Probing synergy between two catalytic strategies in the glycoside hydrolase O-GlcNAcase using multiple linear free energy relationships
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Human O-GlcNAcase plays an important role in regulating the post-translational modification of serine and threonine residues with β-O-linked N-acetylglucosamine monosaccharide unit (O-GlcNAc). The mechanism of O-GlcNAcase involves nucleophilic participation of the 2-acetamido group of the substrate to displace a glycosidically linked leaving group. The tolerance of this enzyme for variation in substrate structure has enabled us to characterize O-GlcNAcase transition states using several series of substrates to generate multiple simultaneous free-energy relationships. Patterns revealing changes in mechanism, transition state, and rate-determining step upon concomitant variation of both nucleophilic strength and leaving group abilities are observed. The observed changes in mechanism reflect the roles played by the enzymic general acid and the catalytic nucleophile. Significantly, these results illustrate how the enzyme synergistically harnesses both modes of catalysis; a feature that eludes many small molecule models of catalysis. These studies also suggest the kinetic significance of an oxocarbenium ion intermediate in the O-GlcNAcase-catalyzed hydrolysis of glucosaminides, probing the limits of what may be learned using nonatomistic investigations of enzymic transition-state structure and offering general insights into how the superfamily of retaining glycoside hydrolases act as efficient catalysts.
- Greig, Ian R.,Macauley, Matthew S.,Williams, Ian H.,Vocadlo, David J.
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supporting information; experimental part
p. 13415 - 13422
(2010/01/16)
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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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- Iminosugar glycoconjugates
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The iminosugar conjugates according to the invention are N-alkylated 1,5-dideoxy-1,5-iminohexitol or 1,5-dideoxy-1,5-iminopentitol derivatives. The iminosugar component can be, for example, D-gluco-, L-ido-, D-galacto-, D-manno-, 2-acetamido-2-deoxy-D-gluco- or xylo-configuration. The N-substituent is a protected L-α-aminoacid derivative, showing L-lysine-like structural features. The linkage between the carbohydrate and the peptide component is not via the usual glycosidic position, but shows structural features of a very stable tertiary amine. Thus the linkage is very stable. These new compounds are synthesised by using catalytic intramolecular reductive amination of dicarbonyl sugars with partially protected amino acids. The process of intramolecular reductive amination itself is carried out using Pearlman's catalyst (Pd(OH)2/C) and H2 at ambient pressure and room temperature. The resulting accessible class of iminosugar conjugate compounds is represented by the general structure shown in Figure 4(c). The alkyl chain length parameter n can be freely chosen from n=0 upwards. Preferably n is between 0 and 10, and more preferably n is 2, 3, or 4. Residue R1 can be chosen from H, OH, or NHAc, with Ac being Acetyl. R2 can be H, OH, or NHAc. R3, R4, R5, R6 can be H or OH. R7 and R8 can be H, CH2OH CH3, COQH, or COOR with R being Alkyl or Aryl. R9 and R10 can be chosen from H, NH2, NHR, with R being a protective group, an amino acid, a peptide, or a protein. R11 can be OH, O-Alkyl, O-Aryl, NH2, N-Alkyl, N-Aryl, amino acid or peptide, connected via an amide bond.
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Page/Page column 5
(2008/06/13)
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- Analysis of PUGNAc and NAG-thiazoline as transition state analogues for human O-GlcNAcase: Mechanistic and structural insights into inhibitor selectivity and transition state poise
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O-GlcNAcase catalyzes the cleavage of β-O-linked 2-acetamido-2-deoxy- β-D-glucopyranoside (O-GlcNAc) from serine and threonine residues of post-translationally modified proteins. Two potent inhibitors of this enzyme are O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) and 1,2-dideoxy-2′-methyl-α-D-glucopyranoso[2,1-d]-Δ2′- thiazoline (NAG-thiazoline). Derivatives of these inhibitors differ in their selectivity for human O-GlcNAcase over the functionally related human lysosomal β-hexosamindases, with PUGNAc derivatives showing modest selectivities and NAG-thiazoline derivatives showing high selectivities. The molecular basis for this difference in selectivities is addressed as is how well these inhibitors mimic the O-GlcNAcase-stabilized transition state (TS). Using a series of substrates, ground state (GS) inhibitors, and transition state mimics having analogous structural variations, we describe linear free energy relationships of log(KM/kcat) versus log(KI) for PUGNAc and NAG-thiazoline. These relationships suggest that PUGNAc is a poor transition state analogue, while NAG-thiazoline is revealed as a transition state mimic. Comparative X-ray crystallographic analyses of enzyme-inhibitor complexes reveal subtle molecular differences accounting for the differences in selectivities between these two inhibitors and illustrate key molecular interactions. Computational modeling of species along the reaction coordinate, as well as PUGNAc and NAG-thiazoline, provide insight into the features of NAG-thiazoline that resemble the transition state and reveal where PUGNAc fails to capture significant binding energy. These studies also point to late transition state poise for the O-GlcNAcase catalyzed reaction with significant nucleophilic participation and little involvement of the leaving group. The potency of NAG-thiazoline, its transition state mimicry, and its lack of traditional transition state-like design features suggest that potent rationally designed glycosidase inhibitors can be developed that exploit variation in transition state poise.
- Whitworth, Garrett E.,Macauley, Matthew S.,Stubbs, Keith A.,Dennis, Rebecca J.,Taylor, Edward J.,Davies, Gideon J.,Greig, Ian R.,Vocadlo, David J.
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p. 635 - 644
(2007/10/03)
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- Synthesis of Tc-99m labeled glucosamino-Asp-cyclic(Arg-Gly-Asp-d-Phe-Lys) as a potential angiogenesis imaging agent
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Angiogenesis imaging agents for single photon emission computed tomography (SPECT) play a role in diagnosing tumor-induced angiogenesis as well as tumor metastasis. We synthesized and evaluated radiolabeled RGD glycopeptides by incorporation of the [
- Lee, Byung Chul,Sung, Hyun Ju,Kim, Ji Sun,Jung, Kyung-Ho,Choe, Yearn Seong,Lee, Kyung-Han,Chi, Dae Yoon
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p. 7755 - 7764
(2008/03/28)
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- A 1-acetamido derivative of 6-epi-valienamine: An inhibitor of a diverse group of β-N-acetylglucosaminidases
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The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of β-N- acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human β-hexosaminidase, as well as two bacterial β-N-acetylglucosaminidases. A 3-D structure of the complex of Bacteroides thetaiotaomicron BtGH84 with the inhibitor shows the unsaturated ring is surprisingly distorted away from its favoured solution phase conformation and reveals potential for improved inhibitor potency. This journal is The Royal Society of Chemistry.
- Scaffidi, Adrian,Stubbs, Keith A.,Dennis, Rebecca J.,Taylor, Edward J.,Davies, Gideon J.,Vocadlo, David J.,Stick, Robert V.
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p. 3013 - 3019
(2008/04/01)
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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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- Microwave-accelerated Fischer glycosylation
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Fischer glycosylation has been used for decades for the synthesis of simple alkyl and aryl glycosides from free sugars. The reaction proceeds under reflux in the presence of catalytic acid with the alcohol as solvent. The main deficiency of this reaction is the long reaction time required. In this study microwave heating has been utilised for the Fischer glycosylation reaction of N-acetyl-d-glucosamine, N-acetyl-d-galactosamine, d-glucose, d-galactose and d-mannose with a variety of alcohols (methanol, ethanol, benzyl alcohol and allyl alcohol). Remarkable acceleration of the glycosylation reactions (minutes compared to hours) over conventional reflux heating was observed with good yields and production of the α-glycoside as the dominant product.
- Bornaghi, Laurent F.,Poulsen, Sally-Ann
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p. 3485 - 3488
(2007/10/03)
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- Carbohydrate-derived aminoalcohol ligands for asymmetric Reformatsky reactions
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Members of a family of functionally and stereochemically diverse d-glucosamine-derived tertiary aminoalcohol ligands have been used to promote the asymmetric Reformatsky reaction. The β-hydroxyester product tert-butyl 3-phenyl-3-hydroxy-propanoate was obt
- Emmerson, Daniel P.G.,Hems, William P.,Davis, Benjamin G.
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p. 213 - 221
(2007/10/03)
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- Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria
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The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.
- Hesek, Dusan,Suvorov, Maxim,Morio, Ken-Ichiro,Lee, Mijoon,Brown, Stephen,Vakulenko, Sergei B.,Mobashery, Shahriar
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p. 778 - 784
(2007/10/03)
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- An efficient synthesis of derivatives of 2-acetamido-4-amino-2,4,6- trideoxy-D-galactopyranose
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Methyl 2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactopyranoside (10) was synthesized from D-glucosamine hydrochloride in eight steps in an overall yield of 31%. Key steps include the selective benzoylation at O-3 of methyl 2-acetamido-2,6-dideoxy-α-D-glucopyranoside in 89% yield and the subsequent Mitsunobu reaction using diphenylphosphoryl azide as the azide source which proceeded in 92% yield. Di- and mono-benzyloxycarbonyl derivatives of 10 were also prepared. Copyright
- Liang, Hong,Grindley
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- Precise structure activity relationships in asymmetric catalysis using carbohydrate scaffolds to allow ready fine tuning: dialkylzinc-aldehyde additions.
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The ready construction of 24 stereochemically and functionally diverse carbohydrate ligand structures from a core D-glucosamine scaffold has allowed the evaluation of broad ranging structure activity relationships in ligand accelerated zincate additions t
- Emmerson, Daniel P G,Villard, Renaud,Mugnaini, Claudia,Batsanov, Andrei,Howard, Judith A K,Hems, William P,Tooze, Robert P,Davis, Benjamin G
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p. 3826 - 3838
(2007/10/03)
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- Stereoselective synthesis of [13C]methyl 2-[15N]amino-2-deoxy-beta-D-glucopyranoside derivatives.
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Efficient syntheses of three [13C]methyl 2-[15N]amino-2-deoxy-beta-D-glucopyranoside derivatives are described. Amination of the D-glucal with (saltmen)Mn(15N) proceeded with 11:1 stereoselectivity favoring the gluco configuration; subsequent methylation of the [15N]lactol using [13C]iodomethane and silver(I) oxide afforded the doubly labeled beta glucoside in high yield. This compound served as the common precursor for three [13C]methyl 2-[15N]aminoglucosides: (2-[15N]trifluoroacetyl-), (2-[15N]acetyl-), and (2-[15N]azido-). Selected heteronuclear coupling constants are reported.
- Boulineau,Wei
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p. 271 - 279
(2007/10/03)
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- Conversion of glucosamine to galactosamine and allosamine derivatives: Control of inversions of stereochemistry at C-3 and C-4
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The reactions of sodium benzoate with a series of trimesylates derived from glucosamine have been examined in an attempt to gain facile access to galactosamine analogues. Trimesylate 17, in which the amino group was protected as a phthalimide, underwent double displacement at positions 4 and 6 to give the dibenzoate 18 with the desired galactosamine configuration. In contrast, trimesylates 21 and 27, in which the amino groups were protected as acetamides, unexpectedly underwent double displacement at positions 3 and 6, giving products 22 and 28, respectively, with allosamine configurations.
- McGeary,Wright,Toth
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p. 5102 - 5105
(2007/10/03)
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