- Synthesis of Dense and Chiral Dendritic Polyols Using Glyconanosynthon Scaffolds
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Most classical dendrimers are frequently built-up from identical repeating units of low valency (usually AB2 monomers). This strategy necessitates several generations to achieve a large number of surface functionalities. In addition, these typical monomers are achiral. We propose herein the use of sugar derivatives consisting of several and varied functionalities with their own individual intrinsic chirality as both scaffolds/core as well as repeating units. This approach allows the construction of chiral, dense dendrimers with a large number of surface groups at low dendrimer generations. Perpropargylated β-D-glucopyranoside, serving as an A5 core, together with various derivatives, such as 2-azidoethyl tetra-O-allyl-β-D-glucopyranoside, serving as an AB4 repeating moiety, were utilized to construct chiral dendrimers using "click chemistry" (CuAAC reaction). These were further modified by thiol-ene and thiol-yne click reactions with alcohols to provide dendritic polyols. Molecular dynamic simulation supported the assumption that the resulting polyols have a dense structure
- Shiao, Tze Chieh,Rej, Rabindra,Rose, Mariécka,Pavan, Giovanni M.,Roy, René
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- Glycosyl-Substituted Dicarboxylates as Detergents for the Extraction, Overstabilization, and Crystallization of Membrane Proteins
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To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl-substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane–cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b, 8 c, and 9 b preserved the ATPase function of BmrA, an ATP-binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a, 8 b, 8 f, 9 a, and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G-protein-coupled adenosine receptor A2AR. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 ?. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs.
- Nguyen, Kim-Anh,Peuchmaur, Marine,Magnard, Sandrine,Haudecoeur, Romain,Boyère, Cédric,Mounien, Saravanan,Benammar, Ikram,Zampieri, Veronica,Igonet, Sébastien,Chaptal, Vincent,Jawhari, Anass,Boumendjel, Ahcène,Falson, Pierre
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- Synthesis, click reaction, molecular structure, spectroscopic and DFT computational studies on 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile
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The compound 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile has been synthesized and confirmed by different characterization techniques such as elemental analysis, IR, UV-vis spectroscopy, and X-ray single-crystal determination. The molecular geometry from X-ray determination of this compound in the ground state has been compared using the Hartree-Fock (HF) and density functional theory (DFT) with the 6-31G(d) basis set. This compound reacted with sugar azide via click reaction to form triazol ring. The synergy between carbohydrate molecule and fluorinated organic compound achieved novel synthetic pathways, properties, and applications in chemistry science.
- Hasan, Muhammad,Shalaby, Mona
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- Polymersome-forming amphiphilic glycosylated polymers: Synthesis and characterization
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Copper-catalyzed azide-alkyne cycloaddition (CuAAC) was used to prepare glycosylated polyethylene (PE)-poly(ethylene glycol) (PEG) amphiphilic block copolymers. The synthetic approach involves preparation of alkyne-terminated PE-b-PEG followed by CuAAC reaction with different azide functionalized sugars. The alkyne-terminated PE-b-PEG was prepared by etherification reaction between hydroxyl-terminated PE-b-PEG (Mn ~ 875 g mol-1) and propargyl bromide and azidoethyl glycosides were prepared by glycosylation of 2-azidoethanol. Atmospheric pressure solids analysis probe-mass spectrometry was used as a novel solid state characterization tool to determine the outcome of the CuAAC click reaction and end-capping of PE-b-PEG by the azidoethyl glycoside group. The aqueous solution self-assembly behavior of these amphiphilic glycosylated polymers was explored by TEM and dye solubilization studies. Carbohydrate-bearing spherical aggregates with the ability to solubilize a hydrophobic dye were observed. The potential of these amphiphilic glycosylated polymers to self-assemble via electro-formation into giant carbohydrate-bearing polymersomes was also investigated using confocal fluorescence microscopy. An initial bioactivity study of the carbohydrate-bearing aggregates is furthermore presented.
- Eissa, Ahmed M.,Smith, Michael J.P.,Kubilis, Artur,Mosely, Jackie A.,Cameron, Neil R.
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- Derivatization of glucose and 2-deoxyglucose for transition metal complexation: Substitution reactions with organometallic 99mTc and re precursors and fundamental NMR investigations
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Synthetic strategies for the bifunctionalization of glucose and 2-deoxyglucose at position C-1 for transition metal coordination are reported. In particular organometallic technetium and rhenium complexes for potential use in diagnostic nuclear medicine w
- Petrig, Jeannine,Schibli, Roger,Dumas, Cecile,Alberto, Roger,Schubiger
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- Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to Epithelial Cells
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Pathogens frequently rely on lectins for adhesion and cellular entry into the host. Since these interactions typically result from multimeric binding of lectins to cell-surface glycans, novel therapeutic strategies are being developed with the use of glycomimetics as competitors of such interactions. Herein we study the benefit of nucleic acid based oligomeric assemblies with PNA–fucose conjugates. We demonstrate that the interactions of a lectin with epithelial cells can be inhibited with conjugates that do not form stable assemblies in solution but benefit from cooperativity between ligand–protein interactions and PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully blocked the binding of the fucose-binding lectin BambL of Burkholderia ambifaria, a pathogenic bacterium, to epithelial cells with an efficiency of more than 700-fold compared to l-fucose.
- Machida, Takuya,Novoa, Alexandre,Gillon, émilie,Zheng, Shuangshuang,Claudinon, Julie,Eierhoff, Thorsten,Imberty, Anne,R?mer, Winfried,Winssinger, Nicolas
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- Synthesis and biodistribution of novel 99mTcN complexes of glucose dithiocarbamate as potential probes for tumor imaging
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In this study, two novel glucose dithiocarbamates (3a and 3b) were successfully synthesized via a "click chemistry" route and then radiolabeled with a [99mTcN]2+ core to prepare the corresponding 99mTcN complexes in high yields. Both of them were hydrophilic and had good in vitro stability. The in vivo biodistribution studies in mice bearing S180 tumor showed that the complexes accumulated in the tumor with high uptake and good retention. Through comparison, 99mTcN-3b had the advantages of higher tumor uptake, tumor/blood and tumor/muscle ratios at 2 h post-injection. The single-photon emission computed tomography (SPECT) image studies of 99mTcN-3b showed obvious radioactive uptake in the tumor region and the tumor-to-non-target ratio was high, suggesting that it could be regarded as a promising tumor imaging agent.
- Liu, Teli,Gan, Qianqian,Zhang, Junbo,Jin, Zhonghui,Zhang, Weifang,Zhang, Yanyan
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- Overcoming hypoxia-induced chemoresistance in cancer using a novel glycoconjugate of methotrexate
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The oxygen and nutrient-deprived tumor microenvironment is considered a key mechanism responsible for cancer resistance to chemotherapy. Methotrexate (MTX) is a widely incorporated chemotherapeutic agent employed in the treatment of several malignancies. However, drug resistance and systemic toxicity limit the curative effect in most cases. The present work aimed to design, synthesize, and biologically evaluate a novel glucose-methotrexate conjugate (Glu-MTX). Our study showed that Glu-MTX exerts an increased cytotoxic effect on cancer cells in comparison to MTX in hypoxia (1% O2 ) and glucose starvation conditions. Furthermore, Glu-MTX was found to inhibit the proliferation and migration of cancer cells more effectively than MTX does. Our results demonstrate that the conjugation of MTX to glucose led to an increase in potency against malignant cells under oxygen and nutrient stress. The observations shed light on a potential therapeutic approach to overcome chemoresistance in cancer.
- Wo?niak, Marta,Pastuch-Gawo?ek, Gabriela,Makuch, Sebastian,Wi?niewski, Jerzy,Zió?kowski, Piotr,Szeja, Wies?aw,Krawczyk, Monika,Agrawal, Siddarth
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- The synthesis of new fluorinated or nonfluorinated sugar phosphonates and phosphoramidates as building blocks in the synthesis of modified hyaluronic acid subunits
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The synthesis of several new fluorinated or nonfluorinated sugar phosphonates and phosphoramidates as building blocks for the synthesis of modified hyaluronic acid subunits is described. These compounds were prepared from d-glucose and d-glucosamine hydro
- Koroniak-Szejn, Katarzyna,Tomaszewska, Joanna,Koroniak, Henryk
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- Thiosugar naphthalene diimide conjugates: G-quadruplex ligands with antiparasitic and anticancer activity
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Glycosyl conjugation to drugs is a strategy being used to take advantage of glucose transporters (GLUT) overexpression in cancer cells in comparison with non-cancerous cells. Its extension to the conjugation of drugs to thiosugars tries to exploit their higher biostability when compared to O-glycosides. Here, we have synthesized a series of thiosugar naphthalene diimide conjugates as G-quadruplex ligands and have explored modifications of the amino sidechain comparing dimethyl amino and morpholino groups. Then, we studied their antiproliferative activity in colon cancer cells, and their antiparasitic activity in T. brucei and L. major parasites, together with their ability to bind quadruplexes and their cellular uptake and location. We observed higher toxicity for the sugar-NDI-NMe2 derivatives than for the sugar-NDI-morph compounds, both in mammalian cells and in parasites. Our experiments indicate that a less efficient binding to quadruplexes and a worse cellular uptake of the carb-NDI-morph derivatives could be the reasons for these differences. We found small variations in cytotoxicity between O-carb-NDIs and S-carb-NDIs, except against non-cancerous human fibroblasts MRC-5, where thiosugar-NDIs tend to be less toxic. This leads to a notable selectivity for β-thiomaltosyl-NDI-NMe2 12 (9.8 fold), with an IC50 of 0.3 μM against HT-29 cells. Finally, the antiparasitic activity observed for the carb-NDI-NMe2 derivatives against T. brucei was in the nanomolar range with a good selectivity index in the range of 30- to 69- fold.
- Belmonte-Reche, Efres,Benassi, Alessandra,Cucchiarini, Anne,Doria, Filippo,Freccero, Mauro,Gabelica, Valerie,Mergny, Jean Louis,Morales, Juan Carlos,Guédin, Aurore,Pe?alver, Pablo,Rosu, Frèdèric
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- Neutral Re(I) Complex Platform for Live Intracellular Imaging
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Luminescent metal complexes are a valuable platform for the generation of cell imaging agents. However, many metal complexes are cationic, a factor that can dominate the intracellular accumulation to specific organelles. Neutral Re(I) complexes offer a more attractive platform for the development of bioconjugated imaging agents, where charge cannot influence their intracellular distribution. Herein, we report the synthesis of a neutral complex (ReAlkyne), which was used as a platform for the generation of four carbohydrate-conjugated imaging agents via Cu(I)-catalyzed azide-alkyne cycloaddition. A comprehensive evaluation of the physical and optical properties of each complex is provided, together with a determination of their utility as live cell imaging agents in H9c2 cardiomyoblasts. Unlike their cationic counterparts, many of which localize within mitochondria, these neutral complexes have localized within the endosomal/lysosomal network, a result consistent with examples of dinuclear carbohydrate-appended neutral Re(I) complexes that have been reported. This further demonstrates the utility of these neutral Re(I) complex imaging platforms as viable imaging platforms for the development of bioconjugated cell imaging agents.
- Bader, Christie A.,Brooks, Doug A.,Brooks, Robert D.,Caporale, Chiara,Gillam, Todd A.,Hickey, Shane M.,Massi, Massimiliano,Morrison, Janna L.,Plush, Sally E.,Sorvina, Alexandra,Stagni, Stefano,Werrett, Melissa V.,Wright, Phillip J.,Zacchini, Stefano
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p. 10173 - 10185
(2021/07/26)
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- Chemo- And regioselective click reactions through nickel-catalyzed azide-alkyne cycloaddition
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Metal-catalyzed cycloaddition is an expeditious synthetic route to functionalized heterocyclic frameworks. However, achieving reactivity-controlled metal-catalyzed azide-alkyne cycloadditions from competing internal alkynes has been challenging. Herein, we report a nickel-catalyzed [3 + 2] cycloaddition of unsymmetrical alkynes with organic azides to afford functionalized 1,2,3-triazoles with excellent regio- and chemoselectivity control. Terminal alkynes and cyanoalkynes afford 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles bearing a 4-cyano substituent, respectively. Thioalkynes and ynamides exhibit inverse regioselectivity compared with terminal alkynes and cyanoalkynes, affording 1,4,5-trisubstituted triazoles with 5-thiol and 5-amide substituents, respectively. Density functional theory calculations are performed for the elucidation of the reaction mechanism. The computed mechanism suggests that a nickellacyclopropene intermediate is generated by the oxidative addition of the alkyne substrate to the Ni(0)-Xantphos catalyst, and the subsequent C-N coupling of this intermediate with an azide is responsible for the chemo- and regioselectivity.
- Baek, Seung-Yeol,Baik, Mu-Hyun,Choe, Wonyoung,Hong, Sung You,Jeon, Ji Hwan,Jeong, Seo Yeong,Kim, Woo Gyum,Nam, Dongsik
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supporting information
p. 3374 - 3381
(2020/05/14)
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- Synthesis of a novel resorcin[4]arene-glucose conjugate and its catalysis of the CuAAC reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles in water
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The Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) in aqueous media using resorcin[4]arene glycoconjugate (RG) is reported. The eight β-d-glucopyranoside moieties constructed on the resorcin[4]arene upper rim provide a pseudo-saccharide cavity that offers a suitable host environment for water-insoluble hydrophobic azido and/or alkyne substrates in water. The utility of RG was established as an efficient inverse phase transfer catalyst for the CuAAC in water as a green approach for the synthesis of 1,4-disubstituted 1,2,3-triazole species. The catalytic utility of RG (1 mol%) was demonstrated in a multicomponent one-pot CuAAC for various azido/alkyne substrates. The RG acts as a molecular host and a micro-reactor resulting in the 1,4-disubstituted 1,2,3-triazoles in excellent yield.
- Husain, Ali A.,Bisht, Kirpal S.
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p. 10109 - 10116
(2019/04/10)
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- Carbohydrate-functionalized N-heterocyclic carbene Ru(ii) complexes: Synthesis, characterization and catalytic transfer hydrogenation activity
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Three Ru complexes containing carbohydrate/N-heterocyclic carbene hybrid ligands were synthesized that were comprised of a triazolylidene coordination site and a directly linked per-acetylated glucosyl (5Glc) or galactosyl unit (5Gal), or a glycosyl unit linked through an ethylene spacer (6). Electrochemical and UV-vis analysis indicate only minor perturbation of the electronic configuration of the metal center upon carbohydrate installation. Deprotection of the carbohydrate was accomplished under basic conditions to afford complexes that were stable in solution over several hours, but decomposed in the solid state. Complexes 5 and 6 were used as pre-catalysts for transfer hydrogenation of ketones under basic conditions, i.e. conditions that lead to in situ deprotection of the carbohydrate entity. The carbohydrate directly influences the catalytic activity of the metal center. Remotely linked carbohydrates (complex 6) induce significantly lower catalytic activity than directly linked carbohydrates (complexes 5Glc, 5Gal), while unfunctionalized triazolylidenes are an order of magnitude more active. These observations and substrate variations strongly suggest that substrate bonding is rate-limiting for transfer hydrogenation in these hybrid carbohydrate/triazolylidene systems.
- Byrne, Joseph P.,Musembi, Pauline,Albrecht, Martin
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p. 11838 - 11847
(2019/08/13)
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- 8-hydroxyquinoline glycoconjugates: Modifications in the linker structure and their effect on the cytotoxicity of the obtained compounds
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Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.
- Krawczyk, Monika,Pastuch-Gawo?ek, Gabriela,Pluta, Aleksandra,Erfurt, Karol,Domiński, Adrian,Kurcok, Piotr
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- Synthesis and Characterization of Novel Fluoro-glycosylated Porphyrins that can be Utilized as Theranostic Agents
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Small molecules with modalities for a variety of imaging techniques as well as therapeutic activity are essential, as such molecules render opportunities to simultaneously conduct diagnosis and targeted therapy, so called theranostics. In this regard, gly
- Arja, Katriann,Elgland, Mathias,Appelqvist, Hanna,Konradsson, Peter,Lindgren, Mikael,Nilsson, K. Peter R.
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p. 495 - 503
(2018/08/17)
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- COMPLEXES FOR INTRACELLULAR IMAGING
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The present disclosure relates to complexes for intracellular imaging and also to methods and kits for intracellular imaging or cell labelling. Certain embodiments of the present disclosure provide a complex comprising a transition metal carbonyl compound
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Paragraph 00268; 00270; 00329; 00331; 00337
(2017/02/24)
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- Nickel-Catalyzed Azide-Alkyne Cycloaddition to Access 1,5-Disubstituted 1,2,3-Triazoles in Air and Water
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Transition-metal-catalyzed or metal-free azide-alkyne cycloadditions are methods to access 1,4- or 1,5-disubstituted 1,2,3-triazoles. Although the copper-catalyzed cycloaddition to access 1,4-disubstituted products has been applied to biomolecular reaction systems, the azide-alkyne cycloaddition to access the complementary 1,5-regioisomers under aqueous and ambient conditions remains a challenge due to limited substrate scope or moisture-/air-sensitive catalysts. Herein, we report a method to access 1,5-disubstituted 1,2,3-triazoles using a Cp2Ni/Xantphos catalytic system. The reaction proceeds both in water and organic solvents at room temperature. This protocol is simple and scalable with a broad substrate scope including both aliphatic and aromatic substrates. Moreover, triazoles attached with carbohydrates or amino acids are prepared via this cycloaddition.
- Kim, Woo Gyum,Kang, Mi Eun,Lee, Jae Bin,Jeon, Min Ho,Lee, Sungmin,Lee, Jungha,Choi, Bongseo,Cal, Pedro M. S. D.,Kang, Sebyung,Kee, Jung-Min,Bernardes, Gon?alo J. L.,Rohde, Jan-Uwe,Choe, Wonyoung,Hong, Sung You
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p. 12121 - 12124
(2017/09/12)
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- GLYCOSIDE DERIVATIVES, PREPARATION THEREOF AND USE THEREOF AS PROSTHETIC GROUPS
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The present invention relates to glycoside-derived compounds, to the processes for preparing same and to the use thereof as prosthetic groups for radiolabelling biomolecules. These compounds are co-azido-alkyl 6-deoxy-6-[18F]-fluoroglycosides of formula (I), in which: k is equal to 2 or 3; n is an integer between 1 and 5; R is independently H or a C1-C5 alkyl group, m being an integer between 0 and 2 if k=2 and m between 0 and 3 if k=3; and X is chosen from the group comprising O, S, CH2 and NR′, in which R′ is independently a C1-C5 alkyl group or an aryl group, including all the stereoisomers thereof.
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Paragraph 0083-0089
(2016/04/02)
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- Preparing method for key intermediate disaccharide compound based on anti-tumor vaccine GM3
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The invention relates to a key intermediate disaccharide compound based on anti-tumor vaccine GM3, and belongs to the technical field of oligose synthesis. The structural formula is as follow: (see the formula in the description). The compound is suitable for research of anti-tumor vaccine GM3 synthesis. The invention further provides a preparing method of the compound, the preparing method is concise in synthesis route, easy to operate, low in raw material cost, high in generality and suitable for synthesizing various oligose compounds, and the glycosylation reaction is high in stereoselectivity.
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Paragraph 0028; 0046; 0047
(2016/10/27)
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- Acidamide ethoxy-β-D-glucoside compound and its preparation method and application (by machine translation)
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This invention involves a kind of amide ethoxy-β-D-glucoside compound and method for preparing the same and application, its general structure shown in formula I, wherein R is selected from straight-chain alkyl. This invention of formula I for the first time shown in the synthesis of the amide ethoxy-β-D-glucoside compounds, and confirmed that the kind of compound, to 2 kinds of tumor cells, human non-small cell lung cancer cells H460 HEP3B and human liver cancer cells with significant inhibitory activity, can be used for the preparation of anti-tumor drug; at the same time, the amides of the invention are ethoxy-β-D-glucoside compound the synthetic route of simple steps, high yield. (by machine translation)
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Paragraph 0034; 0035
(2016/10/27)
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- Synthesis and antibacterial activities of novel tyrocidine A glycosylated derivatives towards multidrug-resistant pathogens
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Glycosylation can have a multifaceted impact on the properties and functions of peptides and plays a critical role in interacting with or binding to the target molecules. Herein, based on the previously reported method for macrocyclic glycopeptide synthesis, two series of tyrocidine A glycosylated derivatives (1a-f and 2a-f) were synthesized and evaluated for their antibacterial activities to further study the structure and activity relationships (SAR). Biological studies showed that the synthetic glycosylated derivatives had good antibacterial activities towards methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. SAR studies based on various glycans and linkages were used to enhance the biochemical profile, resulting in the identification of several potent antibiotics, such as 1f, with a great improved therapeutic index than tyrocidine A.
- Zou, Yan,Zhao, Qingjie,Zhang, Chunmei,Wang, Liang,Li, Wenjuan,Li, Xiang,Wu, Qiuye,Hu, Honggang
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p. 586 - 592
(2015/07/02)
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- VANCOMYCIN-SUGAR CONJUGATES AND USES THEREOF
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The present disclosure relates to vancomycin-sugar conjugates, its stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. The present disclosure also relates to process of preparation of the vancomycin-sugar conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts thereof, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases mediated by bacteria.
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- Cell-penetrating and neurotargeting dendritic siRNA nanostructures
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We report the development of dendritic siRNA nanostructures that are able to penetrate even difficult to transfect cells such as neurons with the help of a special receptor ligand. The nanoparticles elicit strong siRNA responses, despite the dendritic str
- Brunner, Korbinian,Harder, Johannes,Halbach, Tobias,Willibald, Julian,Spada, Fabio,Gnerlich, Felix,Sparrer, Konstantin,Beil, Andreas,M?ckl, Leonhard,Br?uchle, Christoph,Conzelmann, Karl-Klaus,Carell, Thomas
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p. 1946 - 1949
(2015/02/19)
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- Tackling vancomycin-resistant bacteria with 'lipophilic-vancomycin-carbohydrate conjugates'
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Vancomycin, a glycopeptide antibiotic, has long been a drug of choice for life-threatening Gram-positive bacterial infections. Vancomycin confers its antibacterial activity by inhibiting bacterial cell wall biosynthesis. However, over the time, vancomycin has also been rendered ineffective by vancomycin-resistant bacteria (VRB). These bacteria developed resistance to it by alteration of cell wall precursor from D-Ala-D-Ala to D-Ala-D-Lac (vancomycin-resistant Enterococci, VRE), which leads to manifold reduction in the binding constant and results in the loss of antibacterial activity. Herein, we report various vancomycin-sugar analogs, based on a simple design rationale, which exhibit increased binding affinity to VRB, thereby resensitizing VRB to vancomycin. Optimized vancomycin-sugar conjugate exhibited 150-fold increase in affinity for N,N′-diacetyl-Lys-D-Ala-D-Lac compared with vancomycin. This improved binding affinity was also reflected in its antibacterial activity, wherein the MIC value was brought down from 750 to 36 μM against VRE (VanA phenotype). To further sensitize against VRE, we appended lipophilic alkyl chain to optimized vancomycin-sugar conjugate. This lipophilic-vancomycin-sugar conjugate was >1000-fold (MIC=0.7 μM) and 250-fold (MIC=1 μM) more effective against VanA and VanB strains of VRE, respectively, compared with vancomycin. Therefore, this synthetically simple approach could lead to the development of new generation of glycopeptide antibiotics, which can be clinically used to tackle VRB infections.
- Yarlagadda, Venkateswarlu,Konai, Mohini M.,Manjunath, Goutham B.,Ghosh, Chandradhish,Haldar, Jayanta
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p. 302 - 312
(2015/06/02)
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- Synthesis and antifungal activities of N-glycosylated derivatives of Tunicyclin D, an antifungal octacyclopeptide
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A series of glycosylated derivatives of Tunicyclin D were synthesized through a highly efficient and versatile synthetic method. The method is based on solid-phase peptide synthesis using 2-chlorotrityl resin as the solid-phase support and glycosyl amino acids as building blocks. Biological studies of the synthetic Tunicyclin D derivatives showed monosaccharide-containing compounds exhibit improved or similar antifungal activities, whereas the compounds carrying disaccharide glycans, showed much weaker antifungal activities.
- Zhao, Qingjie,Zou, Yan,Guo, Junxiang,Yu, Shichong,Chai, Xiaoyun,Hu, Honggang,Wu, Qiuye
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p. 7780 - 7787
(2014/12/10)
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- Convenient access to carbohydrate - BODIPY hybrids by two complementary methods involving one-pot assembly of "clickable" BODIPY dyes
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Two complementary one-pot, three component synthetic strategies based on copper(I)-catalyzed azide - alkyne cycloadditions (CuAAC) have been developed, which allow the efficient assembly of glycosyl-derived alkynes or azides with highly fluorescent boron-dipyrromethene (BODIPY) cores containing azido or alkyne moieties, respectively. The resulting carbohydrate - BODIPY derivatives display excellent photophysical and laser properties that relate to the spacer (amino group or aromatic ring) employed in each of the synthetic protocols.
- Martinez-Gonzalez, Mayra R.,Urías-Benavides, Arlette,Alvarado-Martínez, Enrique,Lopez, J. Cristobal,Gómez, Ana M.,Del Rio, Mayca,Garcia, Inmaculada,Costela, Angel,Ba?uelos, Jorge,Arbeloa, Teresa,Arbeloa, I?igo Lopez,Pe?a-Cabrera, Eduardo
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p. 5659 - 5663
(2014/10/16)
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- Glycoconjugated Rhenium(I) and 99m-technetium(I) carbonyl complexes from pyridyltriazole ligands obtained by "click chemistry"
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A series of pyridyltriazole ligands containing sugar moieties have been prepared by copper(I)-mediated 1,3-dipolar cycloaddition ("click" reaction) of azides functionalized with D-glucose, D-galactose, D-mannose, D-xylose as well as D-maltose residues, an
- Czaplewska, Justyna A.,Theil, Frank,Altuntas, Esra,Niksch, Tobias,Freesmeyer, Martin,Happ, Bobby,Pretzel, David,Sch?fer, Hendrik,Obata, Makoto,Yano, Shigenobu,Schubert, Ulrich S.,Gottschaldt, Michael
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p. 6290 - 6297
(2015/02/19)
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- Design, synthesis and biological evaluation of azithromycin glycosyl derivatives as potential antibacterial agents
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A series of 11,12-cyclic carbonate azithromycin-4″-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated as antibacterial agents to search for target compounds with excellent activity. The results of preliminary antibacterial tests against eight strains in vitro revealed that all of the title compounds exhibited improved activities with broad spectrum compared with the parent compound. The glycosylated side chains may be the pharmacophores responsible for the improved activity.
- Zhang, Lei,Chai, Xiaoyun,Wang, Baogang,Yu, Shichong,Hu, Honggang,Zou, Yan,Zhao, Qingjie,Meng, Qingguo,Wu, Qiuye
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supporting information
p. 5057 - 5060
(2013/09/12)
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- Solid-phase synthesis of 2-aminoethyl glucosamine sulfoforms
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Mono- and disaccharides of sulfonated glucosamines (GlcN sulfoforms) conjugated to 2-aminoethyl linkers were generated by solid-phase synthesis. Orthogonally protected intermediates were tethered onto tritylated polystyrene resin beads, subjected to amodular sequence of deprotection and sulfonation steps, then cleaved from solid support without degradation of N- or O-sulfate esters using solvolytic conditions, and finally purified by reverse-phase HPLC to afford the title compounds. Copyright Taylor & Francis Group, LLC.
- Liu, Runhui,Wei, Alexander
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experimental part
p. 384 - 419
(2012/08/07)
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- Synthesis And Use Of Glycoside Derivatives of Propofol
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The present invention relates to methods and compositions for the synthesis, production, and use of pro-drug propofol analogs. This invention relates to a method for the production of a broad group of glycosylated propofol carbohydrate derivatives.
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Page/Page column 21
(2012/10/23)
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- SYNTHESIS AND USE OF GLYCOSIDE PRO-DRUG ANALOGS
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The present invention relates to methods and compositions for the synthesis, production, and use of pro-drug analogs. This invention relates to a method for the production of a broad group of glycosylated drugs, including but not limited to propofol, acet
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Page/Page column 84-85
(2012/11/06)
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- Biological evaluation of glucose and deoxyglucose derivatives radiolabeled with [99mTc(CO)3(H2O)3]+ core as potential melanoma imaging agents
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Glucose 9 and 2-deoxyglucose 10 were successfully synthesized and radiolabeled with [99mTc(CO)3(H20) 3]+ intermediate in high yield. The complexes were characterized by HPLC and its stability with his
- Dapueto, Rosina,Castelli, Romina,Fernández, Marcelo,Chabalgoity, José A.,Moreno, María,Gambini, Juan Pablo,Cabral, Pablo,Porcal, Williams
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scheme or table
p. 7102 - 7106
(2012/01/13)
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- Neoglycopeptides through direct functionalization of cysteine
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Neoglycopeptides are readily prepared by direct functionalization of cysteine-containing peptides followed by click triazole formation between the resulting propargylated peptides and protected or free (2-azido)-ethyl gluco-, manno,- and galactopyranosides.
- Vala, Christine,Chrétien, Franoise,Balentova, Eva,Lamandé-Langle, Sandrine,Chapleur, Yves
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body text
p. 17 - 20
(2011/03/18)
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- Carbohydrate-based crosslinking agents: Potential use in hydrogels
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A bis(methacrylamido) derivative of glucose has been used as a crosslinking agent for PHEMA sponges formed by polymerization-induced phase separation. Copyright
- Paterson, Stefan M.,Clark, Jasper,Stubbs, Keith A.,Chirila, Traian V.,Baker, Murray V.
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scheme or table
p. 4312 - 4315
(2012/05/20)
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- Synthesis of functional polymer brushes containing carbohydrate residues in the pyranose form and their specific and nonspecific interactions with proteins
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Three novel N-substituted acrylamide monomers containing different carbohydrate residues, 2'-acrylamidoethyl- α-D-mannopyranoside, 2'-acrylamidoethyl-β-D-glucopyranoside, and 2'-acrylamidoethyl-β-D- galactopyranoside, in the pyranose form were synthesized. The corresponding glycopolymer brushes were prepared on silicon substrates by surface-initiated atom transfer radical polymerization (SI-ATRP) using unprotected glycomonomers. The formation of glycopolymer brushes was well-characterized using ellipsometry, ATR-FTIR, water contact angle analysis, atomic force microscopy analysis, and X-ray photoelectron spectroscopy. The effects of halogen, ligand, and solvent on the polymerization were thoroughly investigated. It was shown that CuCl/CuCl2/tris(2- dimethylaminoethyl)amine (Me6TREN) catalytic system with an optimized ratio of Cu(I)/Cu(II) produced glycopolymer with high molecular weight (Mn = 44-140 kDa) and relatively narrow molecular weight distribution (PDI = 1.4). The dry thickness of resulting glycopolymer brushes (10-36 nm) showed a proportional relationship with the molecular weight of free polymer generated in the solution. The grafting densities of obtained glycopolymer brushes were between 0.12 and 0.17 chains/nm2. The grafting of glycopolymer resulted in highly hydrophilic surface layer with very low water contact angles (10°). The glycopolymer brushes showed ultralow protein adsorption from bovine serum albumin (BSA) and fibrinogen (Fb) solutions. Glycopolymer brushes containing glucose units showed relatively better protection against BSA and Fb adsorption than those brushes containing mannose and galactose units. Synthesized glycopolymer brushes retained specific protein interactions, as evident from the interaction with Concanavalin A (Con A). The interaction of surface-grafted glycopolymer brushes with Con A depended on both the stereochemistry of carbohydrate units and the chemical structures present. In addition, the newly synthesized glycopolymer brushes performed significantly better in comparison with currently available structures in terms of specific protein interactions.
- Yu, Kai,Kizhakkedathu, Jayachandran N.
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experimental part
p. 3073 - 3085
(2011/10/08)
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- Nanostructured styrenic co-polymers containing glucopyranosyl residues and their functionalization
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Sugar-based co-polymers with saccharidic units in stable cyclic form and nanometric morphologies stabilized through crosslinking, adaptable through specific functionalizations to biochemical interaction studies with copper-containing amine oxidases, were synthesized from appropriate monomers and macromonomers. The most promising nanospherical co-polymer obtained, containing β-d-glucopyranosidic units, was employed in functionalization reactions with the help of model molecules, achieving useful transformations mainly at the 6-position and to a minor extent at the 2-position of the saccharidic system.
- Pocci, Marco,Alfei, Silvana,Lucchesini, Francesco,Bertini, Vincenzo,Idini, Barbara
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scheme or table
p. 5684 - 5692
(2009/12/03)
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- Carbohydrate microarrays for assaying galactosyltransferase activity
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Carbohydrate microarrays have been used recently for the rapid analysis of glycan-protein or glycan-cell interactions and for the detection of pathogens. As a demonstration of its significance and versatility, the microarray technology has been applied in this effort to assay glycosyltransferase activities. In addition, carbohydrate microarray based methods have been employed to quantitatively determine binding affinities between lectins and carbohydrates.
- Park, Sungjin,Shin, Injae
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p. 1675 - 1678
(2008/02/02)
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- METHODS AND COMPOSITIONS FOR ENZYME-SPECIFIC ACTIVATION OF CARBOHYDRATE-CONJUGATED PRODRUGS
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Methods for the targeted activation of prodrugs by enzymes, which cleave a linkage between a carbohydrate conjugate and a drug. Means to target the activation of prodrugs to specific cells by linking the enzyme to an antibody molecule. Carbohydrate conjugates of geldanamycin.
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Page/Page column 28
(2008/06/13)
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- A one-step synthesis of azide-tagged carbohydrates: Versatile intermediates for glycotechnology
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Herein we describe a simple and practical methodology for accessing both the α-anomers (D-mannose, N-acetyl-D-glucosamine, N-acetyl-D- galactosamine, D-lactose) and α- and β-anomers (D-glucose, D-galactose, L-fucose) of 2′-azidoethyl and azidotriethylene glycol glycosides using free sugars and Dowex 50 (resin) as an efficient catalyst. These azidoalkyl glycosides are increasingly useful synthetic intermediates for glycotechnology. Georg Thieme Verlag Stuttgart.
- Sanki, Aditya K.,Mahal, Lara K.
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p. 455 - 459
(2007/10/03)
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- Synthesis and enzyme-specific activation of carbohydrate-geldanamycin conjugates with potent anticancer activity
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Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate-geldanamycin conjugates for enzyme-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates was evaluated with β-galactosidase and β-glucosidase. Evidently, glycosylation of C-17-position converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as positive control, showed anticancer activity with IC50 of 70.2-380.9 nM in various cancer cells by β-glucosidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using β-glucosidase specific inhibitor [2,5-dihydroxyniethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose-GA, galactose- and lactose-GA conjugates exhibited much less activity with IC 50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA were incubated with β-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by β-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with β-galactosidase for enzyme-specific activation in tumors to increase tumor selectivity.
- Cheng, Hao,Cao, Xianhua,Xian, Ming,Fang, Lanyan,Cai, Tingwei Bill,Ji, Jacqueline Jia,Tunac, Josefino B.,Sun, Duxin,Wang, Peng George
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p. 645 - 652
(2007/10/03)
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- Fullerene derivative and composition comprising the same
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A fullerene derivative represented by the formula (I): 1[wherein, A is a residue of monosaccharides or disaccharides, and Alk is a lower alkylene group, the group represented by the formula (X): 2is a fullerene residual skeleton, and n is an integral number of 1 or 2]or its salt produces a formulation usable for PDT which has more hydrophilicity and lipophilicity, is expected to have selectivity to tumor cells by cell recognition, shows no toxicity to the cells in a dark place and has a cytocidal effect by light irradiation.
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Page/Page column 2; 5
(2008/06/13)
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- Synthesis of carbamate-containing cyclodextrin analogues
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The one-pot cyclooligomerization of a saccharide-derived p-nitrophenyl carbamate monomer was developed to generate a series of novel carbamate-containing cyclodextrin analogues. The "transcarbamoylation" occurs by initial base-induced activation to the is
- Chong, Pek Y.,Petillo, Peter A.
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p. 1093 - 1096
(2007/10/03)
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- Synthesis of the 2-deoxyisomaltose analogue of acarbose by an improved route to chiral valieneamines
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A 2-deoxyisomaltose analogue of acarbose was stereoselectively synthesised in 11 steps with a total yield of 7% starting from 2,6-dibromo-2,6-dideoxy-D-mannono-1,4-lactone (6). The latter was reduced to the lactol, converted to the methyl glycoside (7) and hydrogenated to the 6-bromo-2,6-dideoxyglycoside (8). Benzylation of the hydroxy groups, elimination of bromine to a 5-ene and Ferrier carbocyclisation gave (2S,3R)-2,3-bisbenzyloxycyclohex-5-enone (12). 1,2-addition of benzyloxymethyl lithium at -110 C gave a 6:1 mixture of tertiary alcohols 13; the (1S) isomer was the major one. Reaction with trichloroacetyl isocyanate gave a carbamate 19, which, when dehydrated to the cyanate, spontaneously underwent [1,3] sigmatropic rearrangement to an isocyanate, which on addition of methanol gave the methylcarbamate 20. Basic hydrolysis of this compound gave (2R,3R,5R)-5-amino-1-benzyloxy-methyl-2,3-bis(benzyloxy)cyclohex-6-ene (22), which could be deprotected to 2-deoxyvalieneamine (5). Reaction with 2-azidoethyl 2,3,4-tri-O-benzyl-6-O-triflyl-α-D-glucopyranoside (34) gave the secondary amine 35, which was completely de-O-protected with sodium in ammonia to give 6-deoxy-6-((1R,3R,4R)-3,4-dihydroxy-5-hydroxymethylcyclohex-5-enylamino)-D- glucose (4), the 2-deoxyisomaltose analogue of acarbose.
- Tagmose, Tina M.,Bols, Mikael
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p. 453 - 462
(2007/10/03)
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