- Improved Synthesis of 1-Glycosyl Thioacetates and Its Application in the Synthesis of Thioglucoside Gliflozin Analogues
-
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)
-
- GOLD COMPOSITIONS AND METHODS OF USE THEREOF
-
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.
- -
-
Paragraph 0064; 0071; 0077
(2020/03/05)
-
- 8-Hydroxyquinoline glycoconjugates containing sulfur at the sugar anomeric position—synthesis and preliminary evaluation of their cytotoxicity
-
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
-
-
- Synthesis and Structure-Activity Relationship Study of Antimicrobial Auranofin against ESKAPE Pathogens
-
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
-
p. 7751 - 7768
(2019/09/10)
-
- POLYMER FOR DELIVERY OF BIOLOGICALLY ACTIVE MATERIALS
-
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.
- -
-
-
- Bivalent glycoconjugates based on 1,5-diazabicyclo[3.3.0]octa-3,6-diene-2,8-dione (“bimane”) as a central scaffold
-
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
-
-
- 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)
-
- Synthesis and anticancer activity of novel NHC-gold(I)-sugar complexes
-
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)
-
- Development of photoswitchable inhibitors for β-galactosidase
-
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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- 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)
- -
-
Paragraph 0009; 0031; 0034-0035
(2018/03/26)
-
- Practical synthesis of latent disarmed S-2-(2-propylthio)benzyl glycosides for interrupted Pummerer reaction mediated glycosylation
-
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
-
supporting information
p. 2381 - 2384
(2017/05/29)
-
- Stereoselective Epimerizations of Glycosyl Thiols
-
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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p. 5802 - 5805
(2017/11/10)
-
- Electron-catalyzed radical perfluoroalkylation of organic sulfides: The serendipitous use of the TMEDA/I2 complex as a radical initiator
-
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)
-
- 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.
-
-
- 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.
- -
-
Paragraph 0056; 0057; 0058; 0059; 0060; 0061
(2016/11/28)
-
- Selective S-deacetylation inspired by native chemical ligation: practical syntheses of glycosyl thiols and drug mercapto-analogues
-
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
-
supporting information
p. 2545 - 2551
(2015/04/22)
-
- Stereoretentive palladium-catalyzed arylation, alkenylation, and alkynylation of 1-thiosugars and thiols using aminobiphenyl palladacycle precatalyst at room temperature
-
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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supporting information
p. 8375 - 8379
(2015/06/02)
-
- Design, synthesis and biological evaluation of novel podophyllotoxin derivatives bearing 4β-disulfide/trisulfide bond as cytotoxic agents
-
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)
-
- 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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- 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)
-
- 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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- 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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- 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)
-
- Synthesis of glycosylthiols and reactivity studies
-
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)
-
- 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
-
scheme or table
p. 6278 - 6283
(2011/10/10)
-
- Design and fabrication of multivalent Gal-containing quantum dots and study of its interactions with asialoglycoprotein receptor (ASGP-R)
-
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
-
supporting information; experimental part
p. 4182 - 4185
(2010/09/12)
-
- Sulfonamide linked neoglycoconjugates-A new class of inhibitors for cancer-associated carbonic anhydrases
-
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
-
experimental part
p. 2913 - 2926
(2010/08/06)
-
- Thiyl glycosylate of olefinic proteins: S-linked glycoconjugate synthesis
-
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)
-
- S-glycosyl primary sulfonamides - A new structural class for selective inhibition of cancer-associated carbonic anhydrases
-
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
-
scheme or table
p. 6421 - 6432
(2010/03/31)
-
- A facile preparation of trehalose analogues: 1,1-thiodisaccharides
-
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.
-
experimental part
p. 1039 - 1045
(2009/09/05)
-
- Application of HOF·CH3CN to the synthesis of glycosyl sulfones
-
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.
-
p. 7426 - 7431
(2008/12/20)
-
- α-S-GalCer: Synthesis and evaluation for iNKT cell stimulation
-
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.
-
supporting information; experimental part
p. 6374 - 6376
(2009/09/30)
-
- 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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- 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 AND USE OF GLYCODENDRIMER REAGENTS
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The present invention relates to a chemically modified mutant protein including a cysteine residue substituted for a residue other than cysteine n a precursor protein, the substituted cysteine residue being subsequently modified by reacting the cysteine residue with a glycosylated thiosulfonate. Also a method of producing the chemically modified mutant protein is provided. The present invention also relates to a glycosylated methanethiosulfonate. Another aspect of the present invention is a method of modifying the functional characteristics of a protein including providing a protein and reacting the protein with a glycosylated methanethiosulfonate reagent under conditions effective to produce a glycoprotein with altered functional characteristics as compared to the protein. In addition, the present invention relates to methods of determining the structure-function relationships of chemically modified mutant proteins. The present invention also relates to synthetic methods for producing thio-glycoses, the thio-glycoses so produced, and to methods for producing glycodendrimer reagents.
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Page/Page column 44; 54; sheet 19
(2010/11/08)
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- REAGENTS AND METHODS FOR THE FORMATION OF DISULFIDE BONDS AND THE GLYCOSYLATION OF PROTEINS
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Methods and reagents for the formation of disulfide bonds, particularly in proteins, peptides and amino acids. The methods and reagents are particularly useful for the controlled glycosylation of proteins, peptides and amino acids. The methods utilise thiosulfonate or selenenylsulfide compounds as reagents or intermediates. Some proteins and peptides comprising selenenylsulfide groups also form part of the invention.
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Page/Page column 21-22
(2010/02/10)
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- Synthesis of a phenyl thio-ss-D-galactopyranoside library from 1,5-difluoro-2,4-dinitrobenzene: Discovery of efficient and selective monosaccharide inhibitors of galectin-7
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The galectins are a family of β-galactoside-binding proteins that have been implicated in cancer and inflammation processes. Herein, we report the synthesis of a library of 28 compounds that was tested for binding to galectins-1, -3, -7, -8N and -9N. An aromatic nucleophilic substitution reaction between 1,5-difluoro-2,4-dinitrobenzene and a galacto thiol gave 5-fluoro-2,4-dinitrophenyl 2,3,4,6-tetra-O-acetyl-l-thio-β-D- galactopyranoside. This versatile intermediate was then modified in a two dimensional manner: either by further substitution of the second fluoride by amines or thiols, or by reduction of the nitro groups and acylation of the resulting amines, or both. Deacetylation then gave a library of aromatic β-galactosides that showed variable inhibitory activity against the different galectins, as shown by screening with a fluorescence-polarisation assay. Particularly efficient inhibitors were found against galectin-7, while less impressive enhancements of inhibitor affinity over methyl β-D-galactopyranoside were found for galectin-1, -3, -8N and -9N. The best inhibitors against galectin-7 showed significantly higher affinity (K d as low as 140 μM) than both β-methyl galactoside (K d 4.8 mM) and the unsubstituted β-phenyl thiogalactoside (non-inhibitory). The best inhibitors against galectin-7 were poor against the other galectins and thus have potential as structurally simple and selective tools for dissecting biological functions of galectin-7. The Royal Society of Chemistry 2005.
- Cumpstey, Ian,Carlsson, Susanne,Leffler, Hakon,Nilsson, Ulf J.
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p. 1922 - 1932
(2007/10/03)
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- The C-glycoside analogue of the immunostimulant α-galactosylceramide (KRN7000): Synthesis and striking enhancement of activity
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Which source provides the better drug? The fully synthetic C-glycoside I (Y=CH2) is about 1000 times more potent against malaria in mice than the corresponding O-glycoside (Y=O), which is derived from a natural product and itself known to show remarkable activity against a wide range of diseases. The results of comparative biological assays emphasize the potential of C-glycosides as therapeutic agents.
- Yang, Guangli,Schmieg, John,Tsuji, Moriya,Franck, Richard W.
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p. 3818 - 3822
(2007/10/03)
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- Glyco-SeS: Selenenylsulfide-mediated protein glycoconjugation - A new strategy in post-translational modification
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Site-selective glycosylation by Se-S-mediated ligation has led to the efficient formation of a wide variety of conjugates 1 without the need for a large excess of the carbohydrate reagent. By this convergent method it was possible to introduce a heptasaccharide glycan selectively, and to perform a multiple site-selective chemical glycosylation of protein. A chemically Cysglycosylated glycoprotein was elaborated enzymatically.
- Gamblin, David P.,Garnier, Philippe,Van Kasteren, Sander,Oldham, Neil J.,Fairbanks, Antony J.,Davis, Benjamin G.
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p. 828 - 833
(2007/10/03)
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- Novel synthesis of 1-thioglycopyranoses via thioiminium salts
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Methanolysis of a glycosylthioiminium salt, which was prepared from the reaction of acetohalogenosugar with thioacetamide, afforded the corresponding per-O-acetylated 1,2-trans-1-thioglycose in good yield after fractional crystallization. This synthetic method is very convenient in operation and proceeds without loss of acetyl groups, as the reaction is carried out under mild and neutral conditions.
- Fujihira, Takayoshi,Chida, Mitsutaka,Kamijo, Haruo,Takido, Toshio,Seno, Manabu
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p. 287 - 292
(2007/10/03)
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- Characterization of some mesogenic alkyl 1-thioglycosides
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A series of dodecyl 1-thio-β-D-glycosides has been synthesized and characterized (DSC, NMR, CP MAS, X-ray diffraction) as possible new marking materials with liquid-crystalline properties. These compounds undergo solid to liquid crystal phase transitions at various temperatures, which depend on the nature of the carbohydrate part of the structure. Their liquid-crystalline phases show extreme shear thinning behaviour.
- Henrissat,Hamer,Taylor,Marchessault, Robert
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p. 1162 - 1165
(2007/10/03)
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- Simple synthesis of 2-thioglycosyl derivatives of pyridine N-oxide
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A new class of "latent" glycosyl donors, 2-thioglycosyl pyridinc N-oxides was synthesized from 1-thiosugar and 2-bromopyridine N-oxide in the reaction of aromatic nucleophilic substitution of halogen.
- Pastuch,Szeja
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p. 227 - 230
(2007/10/03)
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- Synthesis of carbohydrates with an anomeric thiol moiety for elaboration into metabolically stable thioglycosides
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The synthesis of thioglycosides for use as metabolically stable biological probes is an area of continued interest. This paper describes the synthesis of functionalised carbohydrates which contain an anomeric thio group. During the course of this work we have examined the most viable route into compounds such as the specifically functionalised carbohydrates 36 and 37, and have also investigated the usefulness of disulfides as protecting groups for anomeric thiols.
- Kiefel, Milton J.,Thomson, Robin J.,Radovanovic, Milica,Von Itzstein, Mark
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p. 937 - 959
(2007/10/03)
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- INSULIN-LIKE, AND INSULIN-ANTAGONISTIC, CARBOHYDRATE DERIVATIVES. THE SYNTHESIS OF ARYL AND ARALKYL D-MANNOPYRANOSIDES AND 1-THIO-D-MANNOPYRANOSIDES
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A number of novel, aryl and aralkyl D-mannopyranosides and 1-thio-D-mannopyranosides were synthesized for evaluation of insulin-like and insulin-antagonistic properties.The substituted-phenyl α-D-mannopyranosides were prepared by the general procedure of Helferich and Schmitz-Hillebrecht, the substituted-phenyl 1-thio-α-D-mannopyranosides by a method corresponding to the Michael synthesis of aromatic glycosides, and the aralkyl 1-thio-α-D-mannopyranosides by aralkylation of 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranose 15 and subsequent O-deacetylation.Compound (15) was obtained by basic cleavage of the amidino group in 2-S-(tetra)-O-acetyl-α-D-mannopyranosyl)-2-thiopseudourea hydrobromide, the product of the reaction of tetra-O-acetyl-α-D-mannosyl bromide with thiourea.Benzyl 1-thio-β-D-mannopyranoside, obtained by reaction of the sodium salt of 1-thio-β-D-mannopyranose with α-bromotoluene, and benzyl 1-thio-α-L-mannopyranoside were also synthesized, in order to asses the stereospecificity of the biological activites measured.
- Durette, Philippe L.,Shen, Tsung Y.
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p. 261 - 274
(2007/10/02)
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