- Methyl tetra-O-acetyl-α-D-glucopyranuronate: crystal structure and influence on the crystallisation of the β anomer
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Methyl tetra-O-acetyl-β-D-glucopyranuronate (1) and methyl tetra-O-acetyl-α-D-glucopyranuronate (3) were isolated as crystalline solids and their crystal structures were obtained. That of the β anomer (1) was the same as that reported by Root et?al., while anomer (3) was found to crystallise in the orthorhombic space group P212121with two independent molecules in the asymmetric unit. No other crystal forms were found for either compound upon recrystallisation from a range of solvents. The α anomer (3) was found to be an impurity in initially precipitated batches of β-anomer (1) in quantities a crystallographic direction in the absence of the α impurity, while the presence of the α anomer (3) enhanced this elongation.
- Hayes, John A.,Eccles, Kevin S.,Lawrence, Simon E.,Moynihan, Humphrey A.
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Read Online
- Tailored design and synthesis of heparan sulfate oligosaccharide analogues using sequential one-pot multienzyme systems
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Heparan sulfate analogues: Highly efficient one-pot multienzyme (OPME) chemoenzymatic systems for the activation and transfer of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) have been developed. They were applied to the sequential tailored synt
- Chen, Yi,Li, Yanhong,Yu, Hai,Sugiarto, Go,Thon, Vireak,Hwang, Joel,Ding, Li,Hie, Liana,Chen, Xi
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Read Online
- Crystal structure of methyl 1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronate
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The identity of the crystalline product formed by the acetylation of a mixture of methyl α- and β-D-glucopyranuronates has been confirmed as being methyl 1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronate (3), which agrees with the assignment from 1H NMR. The absolute configuration of compound 3 was assigned to agree with the known chirality of the precursor sugar, D-glucono-6,3-lactone.
- Root, Yuriko Y.,Wagner, Timothy R.,Norris, Peter
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Read Online
- Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II
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A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call ‘sugar-tail’ approach. The compounds were evaluated in vitro against a panel of CAs. Compared to their parent compound p-sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II in vitro. All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds 7d, 7 g, 7 h demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.
- Fan, Zhanfang,Guo, Chun,Hou, Zhuang,Li, Chuanchao,Lin, Bin,Liu, Yang,Liu, Yichuang,Wang, Yitong,Zhang, Miao
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p. 383 - 390
(2019/12/30)
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- Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles
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Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators of antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from the site of injection into systemic circulation. Here, we report on the design and synthesis of an amphiphilic polymer-prodrug conjugate of an imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures of 200 nm. The conjugate contains an endosomal enzyme-responsive linker enabling degradation of the vesicles and release of the TLR7/8 agonist in native form after endocytosis, which results in high in vitro TLR agonist activity. In a mouse model, locally administered vesicles provoke significantly more potent and long-lasting immune stimulation in terms of interferon expression at the injection site and in draining lymphoid tissue compared to a nonamphiphilic control and the native TLR agonist. Moreover, the vesicles induce robust activation of dendritic cells in the draining lymph node in vivo.
- Wang, Bi,Van Herck, Simon,Chen, Yong,Bai, Xiangyang,Zhong, Zifu,Deswarte, Kim,Lambrecht, Bart N.,Sanders, Niek N.,Lienenklaus, Stefan,Scheeren, Hans W.,David, Sunil A.,Kiessling, Fabian,Lammers, Twan,De Geest, Bruno G.,Shi, Yang
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supporting information
p. 12133 - 12139
(2020/08/06)
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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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supporting information
p. 1588 - 1596
(2020/02/05)
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- Indole-glucoside substrate and preparation method and application thereof in detection of aerobe vaginitis (AV)
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The invention discloses a glycosyl donor synthetic process, aiming to overcome defects in detection of aerobe vaginitis (AV) by the prior art. Glycosyl donor is connected with chromogen indole to generate glucosides, and an indole-glucoside substrate with good effect, high flexibility, high stability and high specificity is then synthetized. According to inspection standards, as a comparison result between the color rendering property of the synthetized substrate and that of conventional AV detection reagents, the color rendering property of the substrate is superior to that of a Chromagar AVdetection reagent. With innovation of the glycosyl donor synthetic process and the synthetic process of gluocosides by connection for synthesis of the indole-glucoside chromogenic substrate, innovation of extraction and purification and application verification, reaction yield of each stage of products is increased greatly, the products are white nearly, influence from color of the substrate to identification process is reduced, and flexibility and accuracy of AV detection are both improved greatly.
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Paragraph 0016
(2018/09/11)
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- A combinatorial approach towards the synthesis of non-hydrolysable triazole-iduronic acid hybrid inhibitors of human α-l-iduronidase: Discovery of enzyme stabilizers for the potential treatment of MPSI
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Preparation of substituent-diverse, triazole-iduronic acid hybrid molecules by click reaction of an azido iduronic acid derivative with randomly chosen alkynes is described. Library members were screened for their ability to inhibit α-l-iduronidase, and hit molecules and analogues were then investigated for their ability to stabilize rh-α-IDUA in a thermal denaturation study. This work resulted in the discovery of the first small molecules that can be used to stabilize exogenous rh-α-IDUA protein in vitro.
- Cheng, Wei-Chieh,Lin, Cheng-Kun,Li, Huang-Yi,Chang, Yu-Chien,Lu, Sheng-Jhih,Chen, Yu-Shin,Chang, Shih-Ying
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supporting information
p. 2647 - 2650
(2018/03/21)
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- A Mechanism-Based Approach to Screening Metagenomic Libraries for Discovery of Unconventional Glycosidases
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Functional metagenomics has opened new opportunities for enzyme discovery. To exploit the full potential of this new tool, the design of selective screens is essential, especially when searching for rare enzymes. To identify novel glycosidases that employ cleavage strategies other than the conventional Koshland mechanisms, a suitable screen was needed. Focusing on the unsaturated glucuronidases (UGLs), it was found that use of simple aryl glycoside substrates did not allow sufficient discrimination against β-glucuronidases, which are widespread in bacteria. While conventional glycosidases cannot generally hydrolyze thioglycosides efficiently, UGLs follow a distinct mechanism that allows them to do so. Thus, fluorogenic thioglycoside substrates featuring thiol-based self-immolative linkers were synthesized and assessed as selective substrates. The generality of the approach was validated with another family of unconventional glycosidases, the GH4 enzymes. Finally, the utility of these substrates was tested by screening a small metagenomic library.
- Nasseri, Seyed Amirhossein,Betschart, Leo,Opaleva, Daria,Rahfeld, Peter,Withers, Stephen G.
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supporting information
p. 11359 - 11364
(2018/08/28)
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- CONJUGATES COMPRISING SELF-IMMOLATIVE GROUPS AND METHODS RELATED THERETO
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and an active agent. The antibody-drug conjugate may comprise a self- immolative group. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 172; 173
(2017/06/27)
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- COMPOSITIONS AND METHODS RELATED TO ANTI-CD19 ANTIBODY DRUG CONJUGATES
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an anti-CD 19 antibody; a linker; and an active agent. The antibody-drug conjugate may comprise a self-immolative group. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 27; 28
(2017/04/11)
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- COMPOSITIONS AND METHODS RELATED TO ANTI-EGFR ANTIBODY DRUG CONJUGATES
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an anti-epidermal growth factor receptor ("EGFR") antibody; a linker; and an active agent. The antibody-drug conjugate may comprise a self-immolative group. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the drug; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 27; 28
(2017/04/11)
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- CONJUGATES COMPRISING PEPTIDE GROUPS AND METHODS RELATED THERETO
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and at least two active agents. In preferred embodiments, the linker comprises a peptide sequence of a plurality of amino acids, and at least two of the active agents are covalently coupled to side chains of the amino acids. The antibody-drug conjugate may comprise a self-immolative group, preferably two-self-immolative groups. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 182
(2017/08/08)
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- A mechanistic study of the non-oxidative decarboxylation catalyzed by the radical S-adenosyl-l-methionine enzyme BlsE involved in blasticidin S biosynthesis
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Decarboxylation is a fundamentally important reaction in biology and involves highly diverse mechanisms. Here we report a mechanistic study of the non-oxidative decarboxylation catalyzed by BlsE, a radical S-adenosyl-l-methionine (SAM) enzyme involved in blasticidin S biosynthesis. Through a series of biochemical analysis with isotopically labeled reagents, we show that the BlsE-catalyzed reaction is initiated by the 5′-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from a sugar carbon of the substrate cytosylglucuronic acid (CGA), and does not involve a carboxyl radical as has been proposed for 4-hydroxyphenylacetate decarboxylase (HPAD). Our study reveals that BlsE represents a mechanistically new type of radical-based decarboxylase.
- Liu, Lei,Ji, Xinjian,Li, Yongzhen,Ji, Wenjuan,Mo, Tianlu,Ding, Wei,Zhang, Qi
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supporting information
p. 8952 - 8955
(2017/08/15)
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- COMPOUNDS COMPRISING SELF-IMMOLATIVE GROUP
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Provided are compounds comprising a self-immolative group, and the compounds comprising a self-immolative group according to the present invention may include a protein (for example, an oligopeptide, a polypeptide, an antibody, or the like) having substrate-specificity for a target and an active agent (for example, a drug, a toxin, a ligand, a detection probe, or the like) having a specific function or activity.
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Paragraph 0199; 0200
(2016/08/03)
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- A NEW QUINOLINE DERIVATIVE FOR USE IN THE TREATMENT AND PREVENTION OF VIRAL INFECTIONS
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The present invention relates to a quinoline derivative of formula (1) or one of its pharmaceutically acceptable salts. The present invention further relates to said quinoline derivative for medicament and for use in the treatment or prevention of a viral or retroviral infection and in particular AIDS or an AIDS-related condition or Human Immunodeficiency virus (HIV). The present invention also relates to a pharmaceutical composition comprising said quinoline derivative and to the process for preparing it as to a novel intermediate compound.
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Page/Page column 23; 24
(2016/09/26)
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- The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-d-glucuronides to l-iduronides are dependent on the anomeric substituent: Syntheses and DFT calculations
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One of the shortest synthetic routes to l-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected d-glucuronic acid derivative. The epimerization of such C-5 bromides to the l-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the l-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the l-ido and d-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the l-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction.
- Mohamed, Shifaza,Krenske, Elizabeth H.,Ferro, Vito
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p. 2950 - 2960
(2016/03/12)
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- Selective and Sensitive Sensing of Free Bilirubin in Human Serum Using Water-Soluble Polyfluorene as Fluorescent Probe
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The adherence of serum protein on conjugated polymer is a major bottleneck in the application of the latter for selective sensing of small biomolecules in blood serum. In this report, we present new polyfluorenes with d-glucuronic acid appendage that is a nonreceptor for any serum protein, thereby providing a platform for selective sensing of free bilirubin in the clinically relevant range of 50 μmol/L in human blood serum. The appended d-glucuronic acid formed noncovalent interactions with bilirubin, which in conjunction with favorable spectral overlap between the polymers and bilirubin facilitated efficient FRET process in aqueous solutions. Addition of bilirubin resulted in the quenching of the polyfluorene emission with simultaneous appearance of bilirubin emission exhibiting visual emission color change from blue to light green. The polymer remained stable in serum even under severe basic conditions and exhibited high selectivity with visual sensitivity only toward free bilirubin in human serum in the presence of crucial interferences such as hemoglobin, proteins, biliverdin, glucose, cholesterol, and metal ions. Nanomolar sensing of bilirubin could also be demonstrated successfully using one of the d-glucuronic acid appended polymer (PF-Ph-GlcA), which could sense ~150 nm of bilirubin in human serum. The combined role of energy transfer and noncovalent interaction highlights the potential of the new polymer design for highly selective sensing activity in complex biofluids.
- Senthilkumar,Asha
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p. 3449 - 3461
(2015/06/22)
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- CHEMOENZYMATIC SYNTHESIS OF HEPARIN AND HEPARAN SULFATE ANALOGS
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The present invention provides a one-pot multi-enzyme method for preparing UDP-sugars from simple sugar starting materials. The invention also provides a one-pot multi-enzyme method for preparing oligosaccharides from simple sugar starting materials.
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Paragraph 0343; 0344; 0345; 0346
(2014/09/03)
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- Improved and large-scale synthesis of different protected d-glucuronals
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Although different protected d-glucuronals are used as precursors for the preparation of many compounds, standard procedures and large-scale syntheses are still not described in the literature. In the course of the development of different protected d-glucuronyl donors we developed several versatile methods that can be used for fast and reproducible preparation of large amounts of the key intermediates. d-Glucuronolactone was converted to methyl 3,4-di-O-acetyl-d-glucuronal applying a novel one-pot protocol, which allowed for large-scale synthesis. Introduction of silyl and benzyl groups was achieved using optimized procedures. Furthermore 3,4,6-tri-O-acetyl-d-glucal was used as starting material for an improved preparation of benzyl protected d-glucuronal, which significantly accelerates and simplifies similar methods described in the literature.
- Mikula, Hannes,Matscheko, Dominik,Schwarz, Markus,Hametner, Christian,Fr?hlich, Johannes
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- Koenigs-Knorr reaction of fusel alcohols with methyl (1-bromo-2,3,4-tri-O- acetyl-α-d-glucopyranosid)uronate leading to the protected alkyl glucuronides - Crystal structures and high resolution 1H and 13C NMR data
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Crystal structures and high resolution 1H and 13C NMR spectral data for methyl (alkyl 2,3,4-tri-O-acetyl-β-d-glucopyranosid) uronates (alkyl = methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, n-pentyl, 2-methyl-1-butyl and 3-methyl-1-butyl) are presented.
- M?nch, Bettina,Gebert, Antje,Emmerling, Franziska,Becker, Roland,Nehls, Irene
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scheme or table
p. 186 - 190
(2012/05/04)
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- Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases
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Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy classification system cleave a terminal unsaturated sugar from the oligosaccharide products released by extracellular bacterial polysaccharide lyases. This pathway, which is involved in extracellular bacterial infection, has no equivalent in mammals. A novel mechanism for UGL has previously been proposed in which the enzyme catalyzes hydration of a vinyl ether group in the substrate, with subsequent rearrangements resulting in glycosidic bond cleavage. However, clear evidence for this mechanism has been lacking. In this study, analysis of the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute methanol in water, in conjunction with the demonstration that UGL rapidly cleaves thioglycosides and glycosides of inverted anomeric configuration (substrates that are resistant to hydrolysis by classical glycosidases), provides strong support for this new mechanism. A hydration-initiated process is further supported by the observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally, the observation of a small β-secondary kinetic isotope effect suggests a transition state with oxocarbenium ion character, in which the hydrogen at carbon 4 adopts an axial geometry. Taken together, these observations validate the novel vinyl ether hydration mechanism and are inconsistent with either inverting or retaining direct hydrolase mechanisms at carbon 1.
- Jongkees, Seino A. K.,Withers, Stephen G.
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supporting information; experimental part
p. 19334 - 19337
(2012/01/31)
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- Pyrrolo[2,1-c][1,4]benzodiazepine-β-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies
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Pyrrolo[2,1-c][1,4]benzodiazepine-β-glucuronide prodrugs 15a-b, with a potential for selective therapy of solid tumors by PMT and ADEPT have been designed, synthesized and evaluated for selective cytotoxicity in the presence of the enzyme β-glucuronidase. The prodrugs have been found to possess reduced cytotoxicity compared to the parent moieties, and are excellent substrates for the enzyme, exhibiting cytotoxicity selectively in the presence of the enzyme. Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs.
- Kamal, Ahmed,Tekumalla, Venkatesh,Raju,Naidu,Diwan, Prakash V.,Sistla, Ramakrishna
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scheme or table
p. 3769 - 3773
(2009/04/04)
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- X-ray diffraction and high-resolution NMR spectroscopy of methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enopyranuronate
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Single-crystal X-ray diffraction and high-resolution 1H and 13C NMR spectral data for methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enopyranuronate are reported. The 5H4 conformation was found to be the preferred form for this glycal, both in the crystal lattice and in solution. The factors determining the 4H5 ? 5H4 conformational equilibrium for acetylated glycals are discussed.
- Liberek, Beata,Tuwalska, Dorota,Konitz, Antoni,Sikorski, Artur
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p. 1280 - 1284
(2008/02/02)
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- New antifungal flavonoid glycoside from Vitex negundo
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Flavonoids are ubiquitous in photosynthesizing cells and are common part of human diet. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research. Our bioactivity guided fractionation of ethanolic extract of leaves of Vitex negundo resulted in the isolation of new flavone glycoside (4) along with five known compounds 1-3, 5 and 6. All the isolated compounds were evaluated for their antimicrobial activities. The new flavone glycoside 4 and compound 5 were found to have significant antifungal activity against Trichophyton mentagrophytes and Cryptococcus neoformans at MIC 6.25 μg/ml.
- Sathiamoorthy,Gupta, Prasoon,Kumar, Manmeet,Chaturvedi, Ashok K.,Shukla,Maurya, Rakesh
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p. 239 - 242
(2007/10/03)
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- Glucuronic acid-based ulosyl donors for introducing α-d-GlcA and β-d-ManA units
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Practical protocols are described for a five-step conversion of d-glucuronolactone into α-d-arabino-2-ketoglucuronyl bromides, which due to their α-selective or β-specific glycosidation, and gluco- or manno-specific carbonyl reductions of the glucurono-2-ulosides formed, are expedient indirect donor substrates for the efficient introduction of α-d-GlcA or β-d-ManA residues.
- Lergenmueller, Matthias,Lichtenthaler, Frieder W.
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p. 2132 - 2137
(2008/02/10)
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- GLUCOPYRANOSIDES CONJUGATES OF 2-(4-HYDROXY-PHENYL)-1- 4-(2-AMIN-1-YL-ETHOXY)-BENZYL]-1H-INDOL-5-OLS
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This invention provides tissue selective estrogens of formula (I) having structure (I) wherein: R1 and R2 are independently, hydrogen, alkyl chain of 1-6 carbon atoms, benzyl, acyl of 2-7 carbon atoms, benzoyl, (1) or (2); X is hydrogen, alkyl of 1-6 carbon atoms, CN, halogen, trifuoromethyl, or thioalkyl of 1-6 carbon atoms; n = 1-3; with the proviso that at least one of R1 or R2 is (1) or (2); or a pharmaceutically acceptable salt thereof.
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Page/Page column 14
(2010/11/08)
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- Synthesis of methyl 1-O-(4-hydroxymethamphetaminyl)-α-D- glucopyranouronate
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For the purpose of the direct characterization of the intact conjugated form in the urine of a methamphetamine (MA) abuser, 4-hydroxymethamphetamine (4-OHMA) glucuronate, corresponding to one of the metabolites of MA, was synthesized from the commercially available methyl 4-hydroxyphenylacetate.
- Nakajima, Rika,Ono, Machiko,Aiso, Sadakazu,Akita, Hiroyuki
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p. 684 - 687
(2007/10/03)
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- Efficient acetylation of carbohydrates promoted by imidazole
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An efficient per-O-acetylation of carbohydrate derivatives and unprotected reducing sugars promoted by imidazole is reported. The reaction conditions have been successfully employed to acetylate carbohydrate derivatives containing acid-susceptible functional groups. In most of the cases the yields obtained were excellent. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Tiwari, Pallavi,Kumar, Rishi,Maulik, Prakas R.,Misra, Anup Kumar
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p. 4265 - 4270
(2007/10/03)
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- Novel efficient routes to heparin monosaccharides and disaccharides achieved via regio- and stereoselective glycosidation
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A new methodology for the synthesis of heparin building blocks has been developed. We describe novel efficient routes to both L-iduronic acid and D-glucuronic acid acceptors. Glycosylation with thioglycosides donors gave corresponding disaccharides in a regio- and stereoselective fashion. An improved approach to synthesizing azido-glucose thioglycoside donor to render azido-sugar from mannose via nucleophilic substitution is described.
- Yu, Henry N.,Furukawa, Jun-Ichi,Ikeda, Tsuyoshi,Wong, Chi-Huey
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p. 723 - 726
(2007/10/03)
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- Rapid access to uronic acid-based mimetics of Kdn2en from D-glucurono-6,3-lactone
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A concise route to novel mimetics of Kdn2en, based on Δ4-uronic acids, from D-glucurono-6,3-lactone is presented. Uronic acid-based mimetics in which an aliphatic ether (O-glycoside), a thioether (S-glycoside), or acetamide takes the place of the natural C-6 glycerol sidechain of the sialic acid were synthesized from the key intermediate, methyl 2,3,4-tri-O-acetyl-α-D-glucopyranosyluronate bromide. (C) 2000 Elsevier Science Ltd.
- Florio, Pas,Thomson, Robin J.,Von Itzstein, Mark
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p. 445 - 448
(2007/10/03)
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- Synthesis of oligosaccharides related to the HNK-1 antigen: I. Synthesis of selectively protected allyl 3-O-[methyl(β-D-glucopyranosyl)uronate]-β-D-galactopyranoside
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The glycosylation of several mono- and dihydroxyl glycosyl acceptors based on allyl β-D-galactopyranoside with completely acylated glucuronyl bromides under the Helferich reaction conditions was studied in order to develop a method for the preparative synthesis of selectively protected disaccharide β-D-GlcA-(1→3)-β-D-Gal in a form that can be used for further preparation of corresponding glycosyl donors and spacerated derivatives. We found that 1,2-orthoesters were the major primary products of the reaction, and their further conversion into isomeric glycosides depended on pH and can be regulated by the type of molecular sieves used. When Acid Washed Molecular Sieves AW 300 were used, glycosides were predominantly synthesized. No selective formation of the (1→3)-bound disaccharide was observed upon glycosylation of glycosyl acceptors with 2,3- and 3,4-diol groupings. This (1→3)-bound disaccharide was most efficiently synthesized by glycosylation of allyl 4,6-O-benzylidene-2-O-benzoyl-β-D-galactopyranoside with pivaloylated glucuronyl bromide. With acetylated or benzoylated glucuronyl bromides or with pivaloyl glucuronyl imidate, this galactoside can also be glycosylated but with a lower yield of the target (1→3)-bound disaccharide and lower glycosylation regioselectivity.
- Kornilov,Kononov,Zatonskii,Shashkov,Nifant'ev
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p. 597 - 607
(2007/10/03)
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- Synthesis and conformational analysis of linear and cyclic peptides containing sugar amino acids
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Sugar amino acids (SAAs) were designed and synthesized as new non-peptide peptidomimetics utilizing carbohydrates as peptide building blocks. They represent sugar-like ring structures that carry an amino and a carboxylic functional group and have a specific conformational influence on the backbone of peptides due to their distinct substitution patterns in rigid pyranose sugar rings. Five different SAAs (SAA1α, SAA1β, SAA2, SAA3, and SAA4) have been synthesized that show the ability to constrain linear backbone conformations or distinct turn structures. Linear and cyclic peptides involving SAAs have been prepared in solution as well as by solid phase synthesis. SAA1α and SAA2 were incorporated into two linear Leu-enkephalin analogs, replacing the natural Gly-Gly dipeptide. NMR studies provide evidence for the conformation-inducing effect of the carbohydrate moiety. SAA2 and SAA3 have been placed in cyclic hexapeptide analogs of somatostatin; SAA4 was incorporated in a model peptide. The conformation of the cyclic peptides cyclo(-SAA2-Phe-D-Trp-Lys-Thr-), cyclo(-SAA3-Phe-D-Trp-Lys(Boc)-Thr(tBu)-), and cyclo(-SAA4-Ala-D-Pro-Ala-Ala-) have been analyzed by various NMR techinques in combination with distance geometry calculations and subsequent molecular dynamic simulations. The determined solution conformations were compared to representative idealized peptide backbones. SAA2 and SAA3 induce a β-turn structure while SAA4 mimics a γ-turn. Both enkephalin analogs were not active in the guinea pig ileum assay. The somatostatin analog containing SAA2 has an inhibition constant (IC50) of 0.15 μM for the inhibition of the release of growth hormone.
- Von Roedern, Erich Graf,Lohof, Elisabeth,Hessler, Gerhard,Hoffmann, Matthias,Kessler, Horst
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p. 10156 - 10167
(2007/10/03)
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- Glycosyl Phosphites as Glycosylation Reagents: Scope and Mechanism
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The glycosylation reactions with glycosyl phosphites in the presence of catalytic amounts of TMSOTf at low temperature have been studied with different donors and acceptors for the synthesis of several glycosides, including O-glycosides, S-glycosides, C-glycosides, and glycopeptides.Mechanistic investigations of the reactions indicate that the glycosyl phosphite is activated by either TfOH or TMSOTf, depending on how the substrates are mixed.When the acceptor is treated with TMSOTf first, the glycosyl phosphite is activated by the resulting TfOH.The glycosyl phosphite can also be activated by TMSOTf directly.The best result is, however, to mix the acceptor and TMSOTf first, followed by addition of the glycosyl phosphite.
- Kondo, Hirosato,Aoki, Shin,Ichikawa, Yoshitaka,Halcomb, Randall L.,Ritzen, Helena,Wong, Chi-Huey
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p. 864 - 877
(2007/10/02)
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