- Synthesis of cyclodextrin-based carbohydrate clusters by photoaddition reactions
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The syntheses of homogeneous cyclodextrin-based carbohydrate clusters, persubstituted with β-D-thioglucosyl or D-thiolactosyl residues on either (a) the primary face, (b) the secondary face, or (c) both the primary and the secondary faces of their cyclodextrin tori, are described. The key step in the synthetic methodology, namely the attachment of the carbohydrate residues to the cyclodextrin torus, proceeds in moderate-good yields (42-70%) by the photoaddition of thiol groups, positioned at the anomeric centers of the carbohydrate residues, to allyl ether functions on the cyclodextrins. Facile removal of protecting groups then affords the free cluster compounds. Extensive 1-D and 2-D NMR spectroscopic investigations were performed on these compounds to determine their structures and establish their homogeneities, and a brief computer molecular modeling study allowed estimates of the dimensions of the clusters to be determined.
- Fulton,Stoddart
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- Synthesis of tetra-O-acetyl-1-thio-α-D-glucopyranose by reaction of tetra-O-acetyl-α-D-glucopyranosyl bromide with N,N-dimethylthioformamide
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A reaction system was found to prepare tetra-O-acetyl-1-thio-D-glycopyranose in both α and β-forms. Methanolysis of the adduct prepared from the reaction of tetra-O-acetyl-α-D-glucopyranosyl bromide with N,N-dimethylthioformamide afforded the corresponding tetra-O-acetyl-1-thio-D-glucopyranose with an anomer ratio α/β of 52:48 in 98% yield. The anomer mixture was easily separated by column chromatography to obtain the product of α-form. This synthetic method is very convenient to proceed by one-pot reaction under ordinary conditions.
- Fujihira, Takayoshi,Arakawa, Gen,Kamijo, Haruo,Takido, Toshio,Seno, Manabu
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- Synthesis and Biochemical Evaluation of an Artificial, Fluorescent Glucosinolate (GSL)
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The synthesis of the first example of a fluorescent glucosinolate (GSL)–BODIPY conjugate based on an azide-containing artificial GSL precursor (GSL-N3) is reported. Biochemical evaluation of the artificial GSLs revealed that the compounds are converted to the corresponding isothiocyanates in the presence of myrosinase. Furthermore, myrosinase-catalyzed hydrolysis in the presence of plant specifier proteins yielded the expected alternative products, namely nitriles. The easy assembly of the fluorescent GSL–BODIPY conjugate by click chemistry from GSL-N3 holds potential for application as a fluorescence labeling tool to investigate GSL-associated processes.
- Glindemann, Carina Patrizia,Backenk?hler, Anita,Strieker, Matthias,Wittstock, Ute,Klahn, Philipp
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- Surface glycosylation of polymer membrane by thiol-yne click chemistry for affinity adsorption of lectin
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We present a novel approach to constructing glycosylated surface for microporous membrane. Carbohydrate derivative can be facilely bound onto the alkyne-modified membrane surface via thiol-yne click chemistry. The glycosylated membrane surface shows an excellent affinity adsorption to lectin on the basis of carbohydrate-protein recognition. The Royal Society of Chemistry.
- Wang, Cang,Ren, Peng-Fei,Huang, Xiao-Jun,Wu, Jian,Xu, Zhi-Kang
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- One pot synthesis of thio -glycosides via aziridine opening reactions
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A one-pot aziridine opening reaction by glycosyl thiols generated in situ from the corresponding anomeric thio-acetates affords thio-glycosides with a pseudo-disaccharide structure and an N-linked tether. The scope of the one-pot aziridine opening reaction was explored on a series of mono- and disaccharides, creating a class of pseudo-glycosidic compounds with potential for further functionalization. Unexpected anomerization of glycosyl thiols was observed under the reaction conditions and the influence of temperature, base and solvent on the isomerization was investigated. Single isomers were obtained in good to acceptable yields for mannose, rhamnose and sialic acid derivatives. The class of thio-glycomimetics synthesized can potentially be recognized by various lectins, while presenting hydrolytic and enzymatic stability. The nitrogen functionality incorporated in the glycomimetics can be exploited for further functionalization, including tethering to linkers, scaffolds or peptide residues.
- Hribernik, Nives,Tamburrini, Alice,Falletta, Ermelinda,Bernardi, Anna
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p. 233 - 247
(2021/01/14)
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- Large-scale synthesis of thio-glucose-conjugated chlorin E6 for photodynamic therapy
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Chlorin e6 is a heterocycle exhibiting spectral absorption in the 600-700 nm wavelength range used for photodynamic therapy (PDT). Herein, a sugar-conjugated chlorin e6 derivative was synthesized on a large scale. An alkyl spacer was fabricated by controlling the alkoxylation conditions between the thio-sugar and chlorin e6 and thio-glucose-conjugated chlorin e6 was successfully synthesized.
- Hyakumura, Keisuke,Kataoka, Hiromi,Kodama, Shintaro,Masuda, Masato,Narumi, Atsushi,Nomoto, Akihiro,Ogawa, Akiya,Okamoto, Yoshiharu,Osaki, Tomohiro,Tanaka, Mamoru,Yamaguchi, Hiroaki,Yano, Shigenobu,Yoshimura, Tomokazu
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- Improved Synthesis of 1-Glycosyl Thioacetates and Its Application in the Synthesis of Thioglucoside Gliflozin Analogues
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An improved method to synthesize 1-glycosyl thioacetates was developed, where per-O-acetylated glycoses were allowed to directly react with potassium thioacetate (KSAc) in the presence of BF3 ? Et2O in ethyl acetate under mild conditions. This method not only overcomes the disadvantage of the traditional one-step method, which is that the odorous and toxic thioacetic acid has to be used, but also overcomes the disadvantage of the traditional two-step method, which is that the unstable intermediate, glycosyl halide, has to be synthesized from the per-O-acetylated glycose in advance. Based on this, the per-O-acetylated glucosyl disulfide and the per-O-acetylated glucosyl 1-thiol were efficiently synthesized in high yields (91 % and 90 % respectively) starting from per-O-acetylated glycoses in two-step without the need to isolate intermediate products. Through metal-catalyzed cross-coupling of per-O-acetylated glucosyl 1-thiol with aryl-iodide under very mild conditions, two thioglucoside gliflozin analogues were efficiently synthesized in high yields for the first time. These two thioglucoside gliflozin analogues were further confirmed to be stable to hydrolysis of β-glucosidase.
- Dong, Hai,Feng, Guang-Jing,Luo, tao,Lv, Jian,Wang, Shuang-Shuang,Wu, Yuzhou
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p. 2940 - 2949
(2021/07/26)
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- Preparation method and application of peracetyl-protected 1-thioglucose and glucose 1-mercaptan
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The invention belongs to the technical field of medicine and sugar chemical synthesis, and particularly relates to a preparation method and application of peracetyl-protected 1-thioglucose and glucose1-mercaptan. The preparation method comprises the following steps of reacting peracetyl-protected glucose and potassium thioacetate in an organic solvent at the temperature of between normal temperature and 50 DEG C under the catalysis of boron trifluoride diethyl ether for 4-8 hours to obtain peracetyl-protected 1-thioglucose; and dissolving the prepared peracetyl-protected 1-thioglucose in dimethylformamide, and removing thioacetyl by using hydrazine hydrate to obtain peracetyl-protected glucose 1-mercaptan. The peracetyl-protected glucose 1-mercaptan can be used for further preparing auronofen and gliclazide thioglycoside analogues. The method disclosed by the invention is mild in reaction condition, simple and convenient to operate, low in synthesis cost, relatively green and high inyield, the auronofen is a medicine for treating rheumatic arthritis, and the gliflozin thioglycoside analogue is a potential medicine for treating type 2 diabetes mellitus.
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Paragraph 0060-0062
(2021/03/24)
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- 8-Hydroxyquinoline glycoconjugates containing sulfur at the sugar anomeric position—synthesis and preliminary evaluation of their cytotoxicity
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One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell and achieving the desired therapeutic dose. Moreover, the accumulation of the drug in healthy tissue can lead to serious side effects. The way to improve the selectivity of a drug to the cancer cells seems to be its conjugation with a sugar molecule, which should facilitate its selective transport through GLUT transporters (glucose transporters), whose overexpression is seen in some types of cancer. This was the idea behind the synthesis of 8-hydroxyquinoline (8-HQ) derivative glycoconjugates, for which 1-thiosugar derivatives were used as sugar moiety donors. It was expected that the introduction of a sulfur atom instead of an oxygen atom into the anomeric position of the sugar would increase the stability of the obtained glycoconjugates against untimely hydrolytic cleavage. The anticancer activity of new compounds was determined based on the results of the MTT cytotoxicity tests. Because of the assumption that the activity of this type of compounds was based on metal ion chelation, the effect of the addition of copper ions on cell proliferation was tested for some of them. It turned out that cancer cells treated with glycoconjugates in the presence of Cu2+ had a much slower growth rate compared to cells treated with free glycoconjugates in the absence of copper. The highest cytotoxic activity of the compounds was observed against the MCF-7 cell line.
- Erfurt, Karol,Hadasik, Agnieszka,Krawczyk, Monika,Pastuch-Gawo?ek, Gabriela
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- GOLD COMPOSITIONS AND METHODS OF USE THEREOF
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Gold compounds and pharmaceutically acceptable salts thereof are disclosed. Certain compounds and salts are active as antibacterial, antifungal, and/or anti-parasitic agents. The disclosure provides pharmaceutical compositions containing the gold compounds. Methods of using the gold compounds to treat bacterial infections are disclosed.
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Paragraph 0064; 0071; 0077
(2020/03/05)
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- Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides
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We synthesized "glyco-arylopeptides", whose folding structure significantly changes depending on the kind of saccharide in their side chain. The saccharide moiety interacts with the main chain via hydrogen bonding, and the non-natural polypeptides form two well-defined architectures - (P)-31- and (M)-41-helices - depending on the length of the saccharide chains and even the configuration of a single stereo-genic center in the epimers.
- Fujii, Naoka,Haino, Takeharu,Ishido, Yuki,Kanbayashi, Naoya,Okamura, Taka-Aki,Onitsuka, Kiyotaka
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supporting information
p. 2767 - 2770
(2020/03/13)
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- POLYMER FOR DELIVERY OF BIOLOGICALLY ACTIVE MATERIALS
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The present invention mainly relates to a polymer for delivery of biologically active materials, a complex and a method of synthesis thereof. The polymer comprises a poly(ethylene imine) and at least one monomer, each monomer comprising a modified sugar moiety, preferably galactose, comprising a sulphur atom or a nitrogen atom and a chemical moiety comprising a terminal epoxide for linking the polyethylene imine to the monomer, wherein the sulphur atom or the nitrogen atom links the modified sugar moiety to the chemical moiety. The biologically active material is preferably a gene, siRNA, mRNA, or plasmid DNA. Further disclosed is the medical use of said complex in treating a disease caused by a genetic disorder, for example cancer.
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- Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics
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Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.
- Brink?, Anne,Risinger, Christian,Lambert, Annie,Blixt, Ola,Grandjean, Cyrille,Jensen, Henrik H.
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p. 7544 - 7548
(2019/10/08)
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- Synthesis and Structure-Activity Relationship Study of Antimicrobial Auranofin against ESKAPE Pathogens
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Auranofin, an FDA-approved arthritis drug, has recently been repurposed as a potential antimicrobial agent; it performed well against many Gram-positive bacteria, including multidrug resistant strains. It is, however, inactive toward Gram-negative bacteria, for which we are in dire need of new therapies. In this work, 40 auranofin analogues were synthesized by varying the structures of the thiol and phosphine ligands, and their activities were tested against ESKAPE pathogens. The study identified compounds that exhibited bacterial inhibition (MIC) and killing (MBC) activities up to 65 folds higher than that of auranofin, making them effective against Gram-negative pathogens. Both thiol and the phosphine structures influence the activities of the analogues. The trimethylphosphine and triethylphosphine ligands gave the highest activities against Gram-negative and Gram-positive bacteria, respectively. Our SAR study revealed that the thiol ligand is also very important, the structure of which can modulate the activities of the AuI complexes for both Gram-negative and Gram-positive bacteria. Moreover, these analogues had mammalian cell toxicities either similar to or lower than that of auranofin.
- Wu, Bin,Yang, Xiaojian,Yan, Mingdi
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p. 7751 - 7768
(2019/09/10)
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- Bivalent glycoconjugates based on 1,5-diazabicyclo[3.3.0]octa-3,6-diene-2,8-dione (“bimane”) as a central scaffold
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The heteroaromatic fused diazabicyclic “bimane” ring system, discovered four decades ago, is endowed with remarkable chemical and photophysical properties. No carbohydrate derivatives of bimanes have, however, been described thus far. Here we report on the syntheses of a range of bimanes decorated with various glycosyl residues. Mono- and disaccharide residues were attached to syn- or anti-bimane central cores via thio-, disulfido- or selenoglycosidic linkages to obtain novel fluorescent or nonfluorescent glycoconjugates. Cu(I)-catalyzed cycloaddition of glycosyl azides to a bimane diethynyl derivative furnished further bivalent glycoconjugates with sugar residues linked to the central bimane core via 1,2,3-triazole rings. We have determined the crystal and molecular structures of several glycosylated and non-glycosylated bimanes and report fluorescence data for the new compounds.
- Szabó, Tamás,Bényei, Attila,Szilágyi, László
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- Isothiocyanates and Glucosinolates from Sisymbrium officinale (L.) Scop. (“the Singers’ Plant”): Isolation and in vitro assays on the somatosensory and pain receptor TRPA1 channel
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Sisymbrium officinale (L.) Scop. is a wild common plant of the Brassicaceae family. It is known as “the singers’ plant” for its traditional use in treating aphonia and vocal disability. Despite its wide use in herbal preparations, the molecular mechanism of action of S. officinale extracts is not known. The plant is rich in glucosinolates and isothiocyanates, which are supposed to be its active compounds. Some members of this family, in particular allylisothiocyanate, are strong agonists of the transient receptor potential ankyrin 1 (TRPA1) channel, which is involved in the somatosensory perception of pungency as well as in the nociception pathway of inflammatory pain. This study aims to isolate the glucosinolates and isothiocianates from fresh S. officinale to identify the major components and test their activity in in vitro assays with a cloned TRPA1 channel. Samples of cultivated S. officinale have been extracted and the active compounds isolated by column chromatography, HPLC and PTLC. The main components glucoputranjivin, isopropylisothiocyanate and 2-buthylisothiocianate have been tested on TRPA1. The glucosinolates glucoputranjivin and sinigrin turned out to be inactive, while isopropylisothiocyanate and 2-buthylisothiocyanate are potent agonists of TRPA1, with an EC50 in the range of the high potency natural agonists identified so far for this somatosensory channel.
- Borgonovo, Gigliola,Zimbaldi, Nathan,Guarise, Marta,De Nisi, Patrizia,De Petrocellis, Luciano,Moriello, Aniello Schiano,Bassoli, Angela
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- Isopropyl - β - D thio-galactopyranoside synthetic method (by machine translation)
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The present invention provides a kind of isopropyl - β - D thio-galactopyranoside synthetic method, namely the method for synthesis of IPTG. Comprises the following steps: five acetyl galactose as raw materials, with the thiourea reaction to obtain the acetyl S - galactose isothiourea fluoro salt, then with the pyrosulfites reaction to obtain the acetyl S - galactose, with isopropyl bromide reaction, the final deacetyl get the compound goal isopropyl - β - D thio-galactopyranoside. In the whole in the reaction process mainly selects the five acetyl galactose and isopropyl bromide as the raw material, not required to be selected smell, toxic isopropyl mercaptan, effectively avoiding harm to human health and the environment, in addition the invention has simple operation, high yield, purity and the like. Is suitable for industrial production. (by machine translation)
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- Development of photoswitchable inhibitors for β-galactosidase
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Azobenzenes are of particular interest as a photochromic scaffold for biological applications because of their high fatigue resistance, their large geometrical change between extended (trans) and bent (cis) isomer, and their diverse synthetic accessibility. Despite their wide-spread use, there is no reported photochromic inhibitor of the well-investigated enzyme β-galactosidase, which plays an important role for biochemistry and single molecule studies. Herein, we report the synthesis of photochromic competitive β-galactosidase inhibitors based on the molecular structure of 2-phenylethyl β-d-thiogalactoside (PETG) and 1-amino-1-deoxy-β-d-galactose (β-d-galactosylamine). The thermally highly stable PETG-based azobenzenes show excellent photochromic properties in polar solvents and moderate to high photostationary states (PSS). The optimized compound 37 is a strong competitive inhibitior of β-galactosidase from Escherichia coli and its inhibition constant (Ki) changes between 60 nM and 290 nM upon irradiation with light. Additional docking experiments supported the observed structure-activity relationship.
- Rustler, Karin,Mickert, Matthias J.,Nazet, Julian,Merkl, Rainer,Gorris, Hans H.,K?nig, Burkhard
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p. 7430 - 7437
(2018/10/24)
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- Improved Synthesis of Glucosinolates
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Herein we describe an improved synthesis of glucosinolates, in which the quantity and cost of materials have been reduced by approximately an order of magnitude compared to typical literature procedures. This allowed us to produce multiple glucosinolates in 10-25 gram batches using vessel sizes no larger than 0.5 litres.
- Lim, Yi Wee,Ong, Michelle Jui Hsien,Hewitt, Russell J.
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p. 1640 - 1650
(2018/02/06)
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- Synthesis and anticancer activity of novel NHC-gold(I)-sugar complexes
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Gold(I) complexes containing stabilising ligands such as phosphines or N-heterocyclic carbenes (NHCs) are known to be inhibitors of the enzyme thioredoxin reductase (TrxR) and therefore act as potential apoptosis-inducing anticancer drug candidates. The conjugation of biomolecules overexpressed in cancer cells to the gold complexes makes them semi-targeted metabolites. Auranofin, an anti-arthritis agent, encompasses this property and exhibits anti-tumour activities. The synthesis, characterization and biological evaluation of four novel N-heterocyclic carbene-gold(I)-thiosugar complexes derived from glucose, lactose and galactose is reported. The reactions of 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) chloride (NHC?-Au-Cl) with pre-synthesized glycosyl thiols under mildly basic conditions gave the desired NHC-Au-thiosugar complexes in high to excellent yields (79–91%). The complexes retain the strong and redox-active Au-S bond contained in Auranofin. All complexes showed good solubility in biological media and were tested against the NCI 60 cancer cell panel for cytotoxicity. The synthesized NHC?-Au derivatives showed good activity in the medium to low micromolar region, while complex 2 showed activity in the low micromolar to nanomolar region against the tested cell lines. To provide a theoretical structure of 4, computational calculations were carried out based on the crystal structures of NHC-Au-SCN and NHC-Au-S-C6H4OMe.
- Dada, Oyinlola,Sánchez-Sanz, Goar,Tacke, Matthias,Zhu, Xiangming
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p. 2904 - 2908
(2018/06/25)
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- Practical synthesis of latent disarmed S-2-(2-propylthio)benzyl glycosides for interrupted Pummerer reaction mediated glycosylation
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Practical synthetic methods to latent disarmed S-2-(2-propylthio)benzyl (SPTB) glycosides for interrupted Pummerer reaction mediated glycosylation have been discovered. Among them, both coupling reaction of PTB-Cl with glycosyl thiols and BF3·OEt2 promoted reaction of peracylated glycosides with PTB-SH produced peracylated SPTB glycosides in large scales and with high efficiency.
- Xu, Yang,Zhang, Qian,Xiao, Ying,Wu, Pinru,Chen, Wei,Song, Zejin,Xiao, Xiong,Meng, Lingkui,Zeng, Jing,Wan, Qian
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supporting information
p. 2381 - 2384
(2017/05/29)
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- Stereoselective Epimerizations of Glycosyl Thiols
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Glycosyl thiols are widely used in stereoselective S-glycoside synthesis. Their epimerization from 1,2-trans to 1,2-cis thiols (e.g., equatorial to axial epimerization in thioglucopyranose) was attained using TiCl4, while SnCl4 promoted their axial-to-equatorial epimerization. The method included application for stereoselective β-d-manno- and β-l-rhamnopyranosyl thiol formation. Complex formation explains the equatorial preference when using SnCl4, whereas TiCl4 can shift the equilibrium toward the 1,2-cis thiol via 1,3-oxathiolane formation.
- Doyle, Lisa M.,O'Sullivan, Shane,Di Salvo, Claudia,McKinney, Michelle,McArdle, Patrick,Murphy, Paul V.
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supporting information
p. 5802 - 5805
(2017/11/10)
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- Electron-catalyzed radical perfluoroalkylation of organic sulfides: The serendipitous use of the TMEDA/I2 complex as a radical initiator
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Radical initiation for the perfluoroalkylation reaction of sulfides has been performed using the complex [(TMEDA)I·I3] and visible light. This methodology bypasses the use of metal(organo)catalysts where the complex [(TMEDA)I·I3] acts as a good electron donor/reductant radical initiating agent. Biologically relevant sulfides are easily substituted with RF moieties employing a mild and environmentally benign radical strategy starting from readily available RFI.
- Yerien,Barata-Vallejo,Camps,Cristófalo,Cano,Uhrig,Postigo
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p. 2274 - 2282
(2017/07/24)
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- Synthesis methods of glycosyl mercaptan and auranofin
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The present invention discloses synthesis methods of glycosyl mercaptan and auranofin. The glycosyl mercaptan synthesis method comprises: (1) dissolving sulfur acetyl protecting saccharide, mercaptan and a weak alkali in an organic solvent to obtain a raw material mixing liquid; and (2) carrying out a reaction on the raw material mixing liquid for 1-24 h at a room temperature, and carrying out extraction purification on the reaction product to obtain the glycosyl mercaptan. The auranofin synthesis method comprises: A, dissolving 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl mercaptan and triethyl phosphorus gold trichloride in an organic solvent, carrying out an ice bath, adding an aqueous solution of an alkali metal weak acid salt, and continuously stirring to obtain a reaction liquid; and B, carrying out a nucleophilic substitution reaction on the reaction liquid at a room temperature to obtain a crude reaction product, and carrying out extraction purification to obtain the pure auranofin. The method of the present invention has characteristics of mild reaction condition, high yield, good adaptability, and low production cost.
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Paragraph 0056; 0057; 0058; 0059; 0060; 0061
(2016/11/28)
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- A building block approach to the synthesis of a family of S-linked α-1,6-oligomannosides
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The syntheses of α-1,6-S-linked methyl di-, tetra- and hexamannosides are reported. The sulfur linkages are generated through coupling of thiolates (derived from anomeric thioacetates or isothiouronium bromides) with 6-deoxy-6-iodo sugars. Two approaches are detailed that involve [2 + 2 + 2] construction from either the reducing end or the non-reducing end. In constructing from the reducing end, coupling of a disaccharide thioacetate with a 6'-iodo reducing end disaccharide, followed by activation of the resulting tetrasaccharide to a 6'''-iodide, and iterative coupling with the same disaccharide thioacetate afforded the S-linked hexasaccharide, as well as the intermediate di- and tetrasaccharides. On the other hand, construction from the non-reducing end involved coupling of the above disaccharide thioacetate with an anomeric S-trityl protected 6'-iodo disaccharide. The resulting S-trityl tetrasaccharide was converted to a tetrasaccharide thioacetate, which was coupled with the same anomeric S-trityl protected 6'-iodo disaccharide to afford the hexasaccharide, which was elaborated to the methyl thioglycoside. The developed methodology may prove useful for the construction of other S-linked oligosaccharides.
- Belz, Tyson,Williams, Spencer J.
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- Design, synthesis and biological evaluation of novel podophyllotoxin derivatives bearing 4β-disulfide/trisulfide bond as cytotoxic agents
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A novel series of C-4β-disulfide/trisulfide-containing podophyllotoxin derivatives were designed, synthesized, and biologically evaluated for their cytotoxic activities against human cancer cell lines, including KB (Mouth Epidermal Carcinoma Cells) and KB/VCR (Vincristine-resistant Mouth Epidermal Carcinoma Cells). Most of these compounds exhibited promising moderate to good cytotoxic activities. In particular, some of them displayed even superior activities to that of etoposide, especially for KB/VCR cell lines, indicating that introduction of the disulfide/trisulfide moiety would be beneficial for overcoming the multi-drug resistant limitation of etoposide. Moreover, the metabolic evaluation of the most promising compound was further performed to reveal that disulfide bond can be stable in human plasma over 8 hours, indicating good potential of these compounds for in vivo anti-cancer activities.
- Zhu, Shi-Jun,Ying, Hua-Zhou,Wu, Yan,Qiu, Ni,Liu, Tao,Yang, Bo,Dong, Xiao-Wu,Hu, Yong-Zhou
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p. 103172 - 103183
(2015/12/23)
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- Selective S-deacetylation inspired by native chemical ligation: practical syntheses of glycosyl thiols and drug mercapto-analogues
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Glycosyl thiols are useful building blocks for the construction of compounds of biological and synthetic importance. Herein, we report a practical synthetic approach toward the efficient synthesis of glycosyl thiols via chemo- and regioselective S-deacetylation inspired by native chemical ligation. This strategy allows the large scale synthesis of glycosyl thiols by simple purification steps without column chromatography. In addition, deacetylation reagents (DTT) could also be recovered and regenerated by a simple process. Thiol containing taxol and artemisinin analogues were successfully prepared based on this methodology. Finally, auranofin, a glucose-based oral drug used to treat rheumatoid arthritis, was synthesized in concise steps and overall high yields.
- Shu, Penghua,Zeng, Jing,Tao, Jinyi,Zhao, Yueqi,Yao, Guangmin,Wan, Qian
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supporting information
p. 2545 - 2551
(2015/04/22)
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- Stereoretentive palladium-catalyzed arylation, alkenylation, and alkynylation of 1-thiosugars and thiols using aminobiphenyl palladacycle precatalyst at room temperature
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A general and efficient protocol for the palladium-catalyzed functionalization of mono- and polyglycosyl thiols by using the palladacycle precatalyst G3-XantPhos was developed. The C-S bond-forming reaction was achieved rapidly at room temperature with various functionalized (hetero)aryl-, alkenyl-, and alkynyl halides. The functional group tolerance on the electrophilic partner is typically high and anomer selectivities of thioglycosides are high in all cases studied. New sulfur nucleophiles such as thiophenols, alkythiols, and thioaminoacids (cysteine) were also successfully coupled to lead to the most general and practical method yet reported for the functionalization of thiols.
- Bruneau, Alexandre,Roche, Maxime,Hamze, Abdallah,Brion, Jean-Daniel,Alami, Mouad,Messaoudi, Samir
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p. 8375 - 8379
(2015/06/02)
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- Synthesis and characterization of novel cationic lipids derived from thio galactose
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Two double chain cationic lipids QAS Cn -2-S (n = 12, 14) derived from thio galactose and carbamate-linkage tertiary amine were synthesized and their structures were confirmed by MS, TOF-MS, 1H NMR and 13C NMR. The QAS C12-2-S revealed superior surface activity compared with QAS C14-2-S with lower CMC and γCMC. Though Lipo C12-2-S displayed large average particle-size with high polydispersity, positive charged Lipo Cn -2-S can be combined with the negative charged DNA, also negatively stained TEM images confirmed the formation of vesicles. All the above prove that the Lipo Cn -2-S is helpful for gene transfection.
- Qiao, Weihong,Zhou, Min,Luo, Limei
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p. 261 - 268
(2014/03/21)
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- Preparation and X-ray analysis of potassium (2,3-dichlorophenyl) glucosinolate
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There has been much interest in obtaining crystals for crystallographic analysis of biologically active glucosinolates. Crystals of potassium (2,3-dichlorophenyl)glucosinolate were obtained as a dual solvate, containing one methanol and one ethanol molecule of crystallization, K+ C 13H14Cl2NO9S2 - CH3OH C2H5OH. The three-dimensional polymeric network consists of chains containing the potassium ions coordinated and bridged by sugar O atoms, which run parallel to the a axis and are further crosslinked through the sugar molecules. The channels of this network are occupied by the dichlorophenyl substituents and the ethanol and methanol solvent molecules. The structure of the S-(2,3,4,6-tetra-O-acetyl- β-d-glucopyranosyl)-2,3-dichlorophenylacetothiohydroxymate, C 21H23Cl2NO10S, precursor has also been determined and the β-configuration and Z isomer of the thiohydroximate substituent is confirmed.
- Vo, Quan V.,Trenerry, Craige,Rochfort, Simone,White, Jonathan,Hughes, Andrew B.
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p. 588 - 594
(2014/08/18)
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- Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols
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A series of glycosyl hemiacetal derivatives have been transformed into thioglycosides and glycosyl thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium carbonotrithioate. The reaction conditions are reasonably simple and yields were very good.
- Ghosh, Tamashree,Santra, Abhishek,Misra, Anup Kumar
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p. 974 - 982
(2013/07/19)
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- Stereoselective synthesis of β-glycosyl thiols and their synthetic applications
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A significantly fast reaction condition for the exclusive preparation β-glycosyl thiol derivatives has been developed successfully. The reaction condition is one-step, fast, high yielding, highly stereoselective, and requires only benchtop chemicals. Further reaction of glycosyl thiol derivatives with Michael acceptors and alkylating agents furnished thioglycosides and (1,1)-thiolinked trehalose analogs.
- Jana, Manas,Misra, Anup Kumar
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p. 2680 - 2686
(2013/04/24)
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- A total synthesis of (R,S)S-glucoraphanin
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A total synthesis of (R,S)S-glucoraphanin (GRP) has been completed by a novel, simple and convenient method in high overall yield (17% over seven steps). The study describes a method for the synthesis of natural and unnatural (methylsulfinyl)alkyl glucosinolates (GLs) and also opens useful pathways to synthesize GRP as well as other sulfinyl GLs.
- Vo, Quan V.,Trenerry, Craige,Rochfort, Simone,Hughes, Andrew B.
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p. 8731 - 8737
(2013/09/23)
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- Study of carbohydrate-protein interactions using glyco-QDs with different fluorescence emission wavelengths
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QDs with different fluorescence emission wavelengths were coated with galactose, glucose, and lactose respectively. The formulas of glyco-QDs were determined by NMR and ICP-OES, and the interactions between glyco-QDs and PNA lectin were investigated by SPR. The results showed that multivalent presentation achieved by using QDs as the scaffold is an effective way to enhance the carbohydrate-protein interactions. The KD for the interaction of PNA with multivalent glyco-QDs is over 3 × 10 6-fold lower than those with the same free sugars. The specific recognition for the sugar coated on the QDs by lectin is maintained. These sugar-coated QDs could be used as a fluorescent probe to label and identify glycoproteins.
- Yang, Yang,Cui, Xi-Kai,Zhong, Ming,Li, Zhong-Jun
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p. 189 - 194
(2013/01/15)
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- Micelles based on gold-glycopolymer complexes as new chemotherapy drug delivery agents
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Polymeric versions of deacetylated auranofin, a gold complex with a sugar ligand, were prepared by post-modifying RAFT glycopolymers. Micellisation of a block copolymer containing pendant Au(i) units produced nanoparticles with an increased anti-proliferative effect against OVCAR-3 human ovarian carcinoma cells.
- Pearson, Samuel,Scarano, Wei,Stenzel, Martina H.
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p. 4695 - 4697
(2012/06/01)
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- Glycosylated eumelanin building blocks by thioglycosylation of 5,6-diacetoxyindole with an expedient selenium-based dynamic-mixture methodology
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A series of 3-thioglycosylated 5,6-diacetoxyindole derivatives, which are important tools for eumelanin research and application, were prepared through a practical and efficient approach exploiting a dynamic mixture of thioglycoside agents. The strategy is feasible for installing both mono- and disaccharide units and relies on the facile in situ conversion of glycosyl disulfides into the corresponding, more reactive, phenylselenenyl sulfides in the presence of diphenyl diselenide, N-bromosuccinimide (NBS) and tetrabutylammonium bromide (TBAB). An expedient thioglycosidation of 5,6-diacetoxyindole with a dynamic mixture of thioglycosides is described. Copyright
- Adinolfi, Matteo,D'Ischia, Marco,Iadonisi, Alfonso,Leone, Loredana,Pezzella, Alessandro,Valerio, Silvia
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experimental part
p. 4333 - 4338
(2012/09/22)
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- A straightforward synthetic access to symmetrical glycosyl disulfides and biological evaluation thereof
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Symmetrical glycosyl disulfides can be prepared within a few hours from per-O-acetylated precursors via a sequential approach entailing short reactions and no purification of any intermediate. The final thiolate-to-disulfide oxidation step is noticeably accelerated by low amounts of phenyl diselenide under air. Applicability of the strategy to non-saccharidic symmetrical alkyl disulfides has also been examined. A preliminary assay of the cytotoxic activity of symmetrical 1,1′- disulfides was performed on two human tumor cell lines, and a noteworthy activity was recorded for a range of these synthetic compounds.
- Adinolfi, Matteo,Capasso, Domenica,Di Gaetano, Sonia,Iadonisi, Alfonso,Leone, Loredana,Pastore, Antonello
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scheme or table
p. 6278 - 6283
(2011/10/10)
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- Synthesis of glycosylthiols and reactivity studies
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The acid-catalyzed reaction of 1,2-anhydro-3,4,6-tri-O-benzyl-α-d- glucopyranose (7) as glycosyl donor with bis-trimethylsilyl sulfide as acceptor affords the α-thiol. Hence, this sterically hindered S-nucleophile as acceptor should provide with O-glycosyl trichloroacetimidates as glycosyl donors that have nonparticipating groups at C-2, glycosylthiols with the thiol group in axial position. This was confirmed for various donors (4, 16-19) with the exception of the corresponding mannosyl donor (20). However, powerful participating groups at C-2 of the donor (23-28) governed the anomeric selectivity.
- Dere, Ravindra T.,Kumar, Amit,Kumar, Vipin,Zhu, Xiangming,Schmidt, Richard R.
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experimental part
p. 7539 - 7545
(2011/11/29)
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- Sulfonamide linked neoglycoconjugates-A new class of inhibitors for cancer-associated carbonic anhydrases
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The contribution of membrane-bound carbonic anhydrases (CAs) to hypoxic tumor growth and progression in cancer implicates cancer-associated CAs as a promising drug target for oncology. In this paper, we present a new class of sulfonamide-linked neoglycoconjugate that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. We describe the application of novel, yet straightforward, chemistry toward the synthesis of inhibitors that comprise both S-glycosyl sulfenamides and S-glycosyl sulfonamides. We also present the CA inhibition profile of our new neoglycoconjugates, more specifically a library of 30 compounds (3-32) that were designed to optimize both SAR (structure-activity relationship) and SPR (structure-property relationship) characteristics. We show that our approach produces neutral, water-soluble, and potent inhibitors (Kis in the low nanomolar range) that target cancer-associated CAs.
- Lopez, Marie,Bornaghi, Laurent F.,Innocenti, Alessio,Vullo, Daniela,Charman, Susan A.,Supuran, Claudiu T.,Poulsen, Sally-Ann
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experimental part
p. 2913 - 2926
(2010/08/06)
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- The Glc2Man2-fragment of the N-glycan precursor - A novel ligand for the glycan-binding protein malectin?
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The Glcα(1→3)Glcα(1→3)Manα(1→2)Man tetrasaccharide (Glc2Man2-fragment), a substructure of the natural N-glycan precursor, was synthesized. The interaction of this fragment with the protein malectin, a carbohydrate binding protein localized in the endoplasmatic reticulum, was investigated by 1H15N HSQC experiments and isothermal calorimetry. The chemical shift perturbations of nuclei in the protein's backbone caused by the binding of the Glc 2Man2-fragment to malectin suggest a binding mode like the known ligand nigerose. The Royal Society of Chemistry 2010.
- Mueller, Lisa N.,Muhle-Goll, Claudia,Biskup, Moritz B.
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supporting information; experimental part
p. 3294 - 3299
(2010/08/21)
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- Design, Synthesis and in Vivo Evaluation of Sulfhydryl β-D-Glucose Cholesterols as Ligands for Brain Targeting Liposomes
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A novel sulfhydryl-β-D-glucose cholesterol 10a-10f as ligand for brain targeting liposomes was designed and synthesized. 10e was applied to the preparation of liposomal delivery system for achieving the brain-targeted delivery of the model drug tegafur in mice utilizing the glucose transporter member 1 (GLUT1). The results suggest the feasibility to enhance liposome's ability of delivering drug to brain by using the designed compound as liposome ligands.
- Fan, Wei,Yan, Chengyi,Qian, Shan,Yao, Nian,Tang, Lei,Wu, Yong
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p. 281 - 289
(2011/03/18)
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- One-pot synthesis of hyperbranched poly(amido amine) clicked with a sugar shell via Michael addition polymerization and thiol click reaction
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This paper reports the production of glycopolymers via a simple and flexible method. A novel glycopolymer with a hyperbranched poly(amido amine) core and a sugar shell (HPAA-GLc) was synthesized by using thiol-ene click reaction via facile one-pot method. Hyperbranched poly(amido amine) with vinyl terminals was first synthesized by Michael addition polymerization of N,N′-methylene bisacrylamide (MBA) with 1-(2-aminoethyl) piperazine (AEPZ). Subsequently, thiol-ene click reaction between vinyl units of hyperbranched poly(amido amine) and thio-glucose was performed in situ. Based on the NMR result, all the vinyl groups reacted with thiol-glucose in 120 min. Strong photoluminescence emission was observed from the aqueous solution of HPAA-GLc. Science China Press and Springer-Verlag Berlin Heidelberg 2010.
- Yu, Zhiqiang,Cui, Mengmeng,Yan, Junjie,You, Yezi
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experimental part
p. 1663 - 1668
(2011/01/13)
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- Design and fabrication of multivalent Gal-containing quantum dots and study of its interactions with asialoglycoprotein receptor (ASGP-R)
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Multivalent lactose (Lac-QDs)- and galactose (Gal-QDs)- coated CdSeS-ZnS core-shell quantum dots (QDs) were prepared. The formula of the glyco-QDs was determined by nuclear magnetic resonance (NMR) and inductively coupled plasma-optical emission spectrometry (ICP-OES). The uptake of the Gal-containing glyco-QDs by HepG2 cells was investigated. Flow cytometry (FCM) and fluorescence microscopy analysis indicated that the uptake is receptor mediated and selective. The prepared multivalent glyco-QDs could be used to mimic the oligosaccharides in the study of hepatic endocytosis. Furthermore, this type of glyco-QDs can be used as a useful fluorescent probe in cell imaging and analysis of carbohydrate-protein interactions.
- Yang, Yang,Zhao, Yue-Tao,Yan, Ting-Ting,Yu, Min,Sha, Yin-Lin,Zhao, Zhi-Hui,Li, Zhong-Jun
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supporting information; experimental part
p. 4182 - 4185
(2010/09/12)
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- S-glycosyl primary sulfonamides - A new structural class for selective inhibition of cancer-associated carbonic anhydrases
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In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is
- Lopez, Marie,Paul, Blessy,Hofmann, Andreas,Morizzi, Julia,Wu, Quoc K.,Charman, Susan A.,Innocenti, Alessio,Vullo, Daniela,Supuran, Claudiu T.,Poulsen, Sally-Ann
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scheme or table
p. 6421 - 6432
(2010/03/31)
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- Thiyl glycosylate of olefinic proteins: S-linked glycoconjugate synthesis
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Tagged for thiolation: A novel glycoconjugation strategy utilizes a non-natural olefin-containing amino acid (homoallylglycine, Hag) as a "tag" for modification and a photoinitiated hydroglycothiolation reaction that is selective only for the Hag olefinic "tag". Application of this method to a number of model proteins allowed complete and precise site-selective glycosylate generating glycoconjugates that include, for example, virus-like particles displaying up to 180 glycans at preselected positions (see scheme).
- Floyd, Nicola,Vijayakrishnan, Balakumar,Koeppe, Julia R.,Davis, Benjamin G.
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supporting information; experimental part
p. 7798 - 7802
(2010/04/05)
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- A facile preparation of trehalose analogues: 1,1-thiodisaccharides
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The synthesis of 1,1-thiodisaccharide trehalose analogues in good to excellent yields by a Lewis acid (BF3·Et2O)-catalysed coupling of sugar per-O-acetate with thiosugar is described. The reactivity of different sugar per-O-acetates and thiosugars is explored.
- Morais, Goreti Ribeiro,Humphrey, Andrew J.,Falconer, Robert A.
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experimental part
p. 1039 - 1045
(2009/09/05)
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- α-S-GalCer: Synthesis and evaluation for iNKT cell stimulation
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The synthesis and evaluation for iNKT stimulation of α-S-galactosylceramide is reported. Prepared by alkylation of a galactosylthiol, this analog of the potent immunostimulatory agent, KRN7000, did not stimulate iNKT cells either in vitro or in vivo.
- Blauvelt, Marisa L.,Khalili, Maryam,Jaung, Weonjoo,Paulsen, Janet,Anderson, Amy C.,Brian Wilson,Howell, Amy R.
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supporting information; experimental part
p. 6374 - 6376
(2009/09/30)
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- Application of HOF·CH3CN to the synthesis of glycosyl sulfones
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A fast, complete and clean conversion of thioglycosides into glycosyl sulfones under mild acidic conditions is described, using the HOF·CH3CN complex at room temperature. This methodology affords glycosyl sulfones in high yields and in excellent purity.
- Morais, Goreti Ribeiro,Humphrey, Andrew J.,Falconer, Robert A.
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p. 7426 - 7431
(2008/12/20)
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- Novel drug delivery compositions
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The present invention provides for a novel molecules useful for delivery of compounds to a mammal, more particularly for the intracellular delivery of nucleotides, nucleotide analogues or compounds with a heterocyclic base. Also provided for are novel therapeutic complexes comprising novel molecules complexed with nucleotide analogues or heterogeneous or homogenous oligomers comprised of nucleotide analogues.
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Page/Page column 10
(2010/11/25)
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- Synthesis of positional thiol analogs of β-D-galactopyranose
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Approaches toward the synthesis of thio-β-D-galactose derivatives are described. These compounds were prepared from the parent carbohydrates: D-galactose, methyl β-D-galactoside and methyl β-D-glucoside, respectively. It was found that not only the strategies of protecting group introduction and selective deprotection, but also the choices of solvent and nucleophilic reagent concentration were crucial to allow the efficient introduction of sulfur at different positions of the galactose ring. The effects from the solvent, the nucleophilic reagent concentration, and the protecting group patterns have been investigated. The results clearly show that ester protecting groups play highly important roles for the synthesis of thio-containing carbohydrates, requiring nonpolar solvents to suppress the neighboring group participation. For the Lattrell-Dax (nitrite-mediated) inversion reaction, employed in the synthetic route to the 2-thio-β-D- galactoside, intramolecular nucleophilic attack, as well as stronger stereospecific ester activation, are necessary to overcome hindrance from 4,6-O-benzylidene protection. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Pei, Zhichao,Dong, Hai,Caraballo, Remi,Ramstroem, Olof
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p. 4927 - 4934
(2008/03/14)
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- Synthesis and structure of novel sugar-substituted bipyridine complexes of rhenium and 99m-technetium
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Novel ligands have been obtained from the reaction of 4.4′- dibromomethyl-2.2′-bipyridine with 2,3.4.6-tetra-O-acetyl-β-D- glucopyranosylthiol. 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosylthiol or 2,3,4,6-tetra-O-acetyl-α-D-thioacetylmannopyranoside in which the sugar residues are thioglycosidically linked to the bipyridinc in the 4,4′-position. Cleavage of the acetyl groups affords hydrophilic symmetric ligands with free hydroxyl groups. Reaction of the new glycoconjugated ligands (L) with [Re(CO)5Cl] yields fluorescent complexes of general formula [Re(L)-(CO)3Cl]. which were characterised by mass spectrometry, elemental analysis and 1H and 11CNMR. IR. UV/Vis and fluorescence spectroscopy. These complexes exhibit excellent solubility and stability in organic solvents or water, depending on the residues of the sugar. One complex, namely tricarbonyl-4,4′-bis[(2.3.4,6-tetra-O-acetyl-β-D- glycopyranosyl)thiomethyl]-2,2′-bipyridinerhe-niumtricarbonylo chloride, has been characterised by X-ray crystallography. A non-symmetric structure of the complexes could be assigned. Radio-labelling of the unprotected ligands with [99mTc(H2O)3(CO)3]+ affords the corresponding water-soluble technetium complexes (in quantitative yields), which were characterised by their HPLC radiation traces. The formed complexes are stable for several hours in the presence of histidine but show partial ligand-exchange after one day.
- Gottschaldt, Michael,Koth, Daniel,Mueller, Dirk,Klette, Ingo,Rau, Sven,Goerls, Helmar,Schaefern, Bernhard,Baum, Richard P.,Yano, Shigenobu
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p. 10273 - 10280
(2008/09/18)
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- The direct formation of glycosyl thiols from reducing sugars allows one-pot protein glycoconjugation
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(Figure Presented) Sweet and easy: A one-pot method consisting of direct thionation (1) followed by thiol-mediated chemoselective ligation (2) can be used for site-selective protein glycosylation. This procedure, which uses the Lawesson reagent, has been shown to be fully compatible with unprotected sugars, the products of which can be directly used in a selenenylsulfide protein glycosylation strategy.
- Bernardes, Goncalo J. L.,Gamblin, David P.,Davis, Benjamin G.
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p. 4007 - 4011
(2007/10/03)
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