- Immobilization of glycoconjugate polymers on cellulose membrane for affinity separation
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Membranes with immobilized glycoconjugate polymers were prepared and lectin adsorption was evaluated. Glycoconjugate polymers having the carbohydrates, lactose, and mannose, the amino groups of the reaction point, and a fluorescence label were synthesized, while cellulose membranes were carboxymethylated. The content of the carboxyl group was evaluated by titration. Subsequently, the glycoconjugate polymers were immobilized on the cellulose membranes by amide linkages formed by condensation reaction. Analysis of the luminescence of the fluorescence labels revealed that the glycoconjugate polymers had been immobilized on the cellulose membranes. Examination of lectin adsorption by the glycoconjugate polymer on the membrane revealed that the membrane with the immobilized mannose-having polymer adsorbed 53% of the applied ConA and the membrane with the immobilized lactose-having polymer adsorbed 83% of the applied RCA120. The membrane with immobilized glycoconjugate polymers selectively adsorbed each lectin. In addition, membranes with different types of immobilized glycoconjugate polymers were used in stacks, and in this case, the membranes selectively adsorbed lectin. Thus, membranes with immobilized glycoconjugate polymers efficiently and easily purify lectin.
- Miyagawa, Atsushi,Kasuya, Maria Carmelita Z.,Hatanaka, Kenichi
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- A new efficient method for catalytic hydrolysis of thioglycoside
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A new and efficient method for catalytic hydrolysis of thioglycosides was successfully developed. Various thioglycosides were smoothly hydrolyzed to afford the corresponding 1-hydroxy sugars in high yields. The hydrolysis of disaccharides was took place smoothly without accompanying no anomerization of existing glycosidic bond.
- Uchiro, Hiromi,Wakiyama, Yoshinari,Mukaiyama, Teruaki
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- Synthesis, chemical characterization and antimicrobial activity of new acylhydrazones derived from carbohydrates
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A new series of glycosylated acylhydrazones was synthesized and all the chemical structures were confirmed by High Resolution Mass Spectrometry (HRMS), 1H and 13C Nuclear Magnetic Resonance (1H-NMR; 13C-NMR) and Fourier Transform Infrared (FTIR) spectroscopy methods. The mass accuracy between the calculated and found values observed in HRMS analyses were near or lower than 5 ppm, which are acceptable for proposing a molecular formula using this technique. All of the synthesized compounds were screened for their antibacterial, antifungal and antiviral activities. Five compounds (12, 13, 14, 16 and 19) exerted a modest antifungal activity against the strains evaluated. Derivative 14 showed fungicidal activity against Candida glabrata at 173.8 μM and saccharide unit contributed to the increase of the antifungal potential against this strain. New chemical manipulation of derivative 14 can make it possible to obtain new potentially antimicrobial agents.
- Guilherme, Fernanda Dias,Simonetti, Julia évelin,Folquitto, Lais Regina Santos,Reis, Adriana Cotta Cardoso,Oliver, Josidel Concei??o,Dias, Amanda Latércia Tranches,Dias, Danielle Ferreira,Carvalho, Diogo Teixeira,Brand?o, Geraldo Célio,Souza, Thiago Belarmino de
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- Microbial mannosidation of bioactive chlorogentisyl alcohol by the marine-derived fungus Chrysosporium synchronum
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The biological transformation of the biologically active chlorogentisyl alcohol (1), isolated from the marinederived fungus Aspergillus sp., was studied. Preparative-scale fermentation of chlorogentisyl alcohol with marine-derived fungus Chrysosporium synchronum resulted in the isolation of a new glycosidic metabolite, 1-O-(α-D-mannopyranosyl)chlorogentisyl alcohol (2). The stereostructure of the new metabolite obtained was assigned on the basis of detailed spectroscopic data analyses, chemical reaction, and chemical synthesis. Compounds 1 and 2 exhibited significant radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) with IC50 values of 1.0 and 4.7 μM, respectively. The compounds 1 and 2 were more active than the positive control, L-ascorbic acid (IC50, 20.0 μM).
- Yun, Keumja,Kondempudi, Chinni Mahesh,Choi, Hong Dae,Kang, Jung Sook,Son, Byeng Wha
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- An efficient method for the preparation of glycosides with a free C-2 hydroxyl group from thioglycosides
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A new and efficient method to produce glycosides with a free C-2 hydroxyl group through 1,2-acyl group migration which occurs during the hydrolysis of 4,6-benzylidene protected thioglycosides has been developed. The acyl transfer products allow for further elaboration.
- Yu, Hai,Ensley, Harry E.
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- Regioselective hydrolysis of different peracetylated β-monosaccharides by immobilized lipases from different sources. Key role of the immobilization
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The effect of the immobilization strategy on the activity, specificity and regioselectivity of three different lipases [those from Thermomyces lanuginose (TLL), Aspergillus niger (ANL) and Candida antarctica B (CAL-B)] in the hydrolysis of peracetylated β-monosaccharides has been evaluated. Three very different immobilization strategies were utilized, covalent attachment, anionic exchange and interfacial activation on a hydrophobic support. The octyl-TLL immobilized preparation was the most efficient biocatalyst in the hydrolysis of 1,2,3,4,6-pentaO-acetyl-β-D-galactopyranose, producing specifically 6-hydroxy-l,2,3,4-tetra-O-acetyl-β-D-galactopyranose in 95 % overall yield, whereas the CNBr-TLL preparation was 48 times slower and regioselective towards the anomeric position, producing the 1-hydroxy derivative in 70% yield. The PEI-TLL immobilized preparation was the most efficient catalyzing the hydrolysis of 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose, permitting us to obtain up to 70% of the 6-hydroxy product. In the hydrolysis of 2-acetamido2-deoxy-l,3,4,6-tetra-0-acetyl-β-D-glucopyranose, the octyl-CALB preparation was not selective at all for the production of monohydroxy products whereas when CAL-B was immobilized on PEI-agarose, the enzyme was highly specific and regioselective producing the 6-hydroxy-2- acetamido-2-deoxy-l,3,4-tri-O-acetyl-β-D-glucopyranose in 70 % yield.
- Palomo, Jose M.,Filice, Marco,Fernandez-Lafuente, Roberto,Terreni, Marco,Guisan, Jose M.
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- Low-budget 3D-printed equipment for continuous flow reactions
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This article describes the development and manufacturing of lab equipment, which is needed for the use in flow chemistry. We developed a rack of four syringe pumps controlled by one Arduino computer, which can be manufactured with a commonly available 3D printer and readily available parts. Also, we printed various flow reactor cells, which are fully customizable for each individual reaction. With this equipment we performed some multistep glycosylation reactions, where multiple 3D-printed flow reactors were used in series.
- Neumaier, Jochen M.,Madani, Amiera,Klein, Thomas,Ziegler, Thomas
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- Synthesis of oligomeric mannosides and their structure-binding relationship with concanavalin A
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Small glycodendrimers with α-mannosyl ligands were synthesized by using copper-catalyzed azide-alkyne coupling chemistry and some of these molecules were used as multivalent ligands to study the induction of concanavalin A (Con A) precipitation. The results showed that the monovalent mannose ligand could induce the precipitation of Con A. This unexpected finding initiated a series of studies to characterize the molecular basis of the ligand-lectin interaction. The atypical precipitation is found to be specific to the mannose, fluorescein moiety (FITC), and Con A. Apparently the mannose ligand binds to Con A through hydrogen-bonding interactions, whereas the binding of FITC is mediated by hydrophobic forces. Being precipitate: A series of glycodendrimers with α-mannosyl ligands were prepared and used to explore the precipitation of concanavalin A (Con A). Surprisingly, the monovalent mannose ligand induced Con A precipitation, which led to an investigation of the molecular basis of the ligand-lectin interaction (see figure).
- Li, Chen-Wei,Hon, Kai-Wei,Ghosh, Bhaswati,Li, Po-Han,Lin, Hsien-Ya,Chan, Po-Han,Lin, Chun-Hung,Chen, Yu-Chie,Mong, Kwok-Kong Tony
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- Expeditious and convenient synthesis of pregnanes and its glycosides as potential anti-dyslipidemic and anti-oxidant agents
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A series of new pregnane derivatives and its glycosides were synthesized in order to find new 'leads' against some important targets. The 3β-hydroxy-16α-(2-hydroxy ethoxy) pregn-5-en-20-one (5) was synthesized from 3β-hydroxy-5,16-pregnadiene-20-one (2) by adopting general modified procedure using BF3:Et2O as a catalyst. Reduction of 5, with sodium borohydride yielded 3β,20β-dihydroxy-16α-(2-hydroxy ethoxy) pregn-5-en (7) as the major isolable product. O-alkylation of the C-20-oxime-pregnadiene (9) with 1,5-dibromopentane yielded 20-(O-5-bromopentyl)-oximino-3β-hydroxy-pregn-5,16-diene (11). Synthesis of C-16 substituted pregnane glycosides (20) and (21) were accomplished with the imidate method using BF3:Et2O. The synthesis of 4-chlorobenzoate (3) and 2-chlorobenzoate (4), derivatives of 2 were also accomplished. These compounds were evaluated for their anti-dyslipidemic and anti-oxidant activity and amongst them compounds 3 and 7 showed more lipid lowering and anti-oxidant activity.
- Sethi, Arun,Maurya, Atul,Tewari, Vibha,Srivastava, Sanjay,Faridi, Shaheen,Bhatia, Gitika,Khan,Khanna,Saxena
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- A solid phase reagent for the capture phosphorylation of carbohydrates and nucleosides.
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[figure: see text] A 1% cross-linked divinylbenzene-polystyrene copolymer, containing cyanoethoxy N,N-diisopropylamine phosphine was prepared as a phosphitylating agent. The polymer-bound phosphitylated precursor was subjected to reaction with alcohols in the presence of 1H-tetrazole to produce the corresponding polymer-bound phosphite triesters. These were then oxidized with tert-butyl hydroperoxide to give the polymer-bound monophosphate triesters. Removal of cyanoethoxy on the resin with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) followed by basic cleavage of the p-hydroxybenzyl linker products yielded monophosphate derivatives.
- Parang,Fournier,Hindsgaul
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- Synthesis and antitumor activity of new shikonin glycosides
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Eleven shikonin glycosides were synthesized and evaluated for their antitumor activity in vitro. Some of them were found to exhibit cytotoxic activities against both drug sensitive cell lines (K562, MCF-7 and HL60) and their drug resistant cell sublines (K562/ADR, MCF-7/ADR and HL60/ADR).
- Su, Yehua,Xie, Jiansheng,Wang, Yanguang,Hu, Xun,Lin, Xianfu
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- Structurally diverse disaccharide analogs of antifreeze glycoproteins and their ability to inhibit ice recrystallization
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The β-D-galactosyl-(1,3)-α-N-acetyl-D-galactosamine disaccharide is present in antifreeze glycoproteins (AFGPs). Analogs of this disaccharide including the β-linked (1,3)-, (1,4)-, and (1,6)-galactosyl-N-acetyl galactosamine and the β-(1,3)-galactosyl-galactoside were synthesized and evaluated for ice recrystallization inhibition (IRI) activity. The results from this study demonstrate that the b-linked-(1,4) disaccharide exhibits more potent IRI activity than the native b-linked-(1,3) disaccharide. The C2 N-acetyl group of the disaccharide does not affect IRI activity but in monosaccharides, the presence of the C2 N-acetyl group decreases IRI activity. The current study will facilitate the design of potent small-molecule ice recrystallization inhibitors.
- Balcerzak, Anna K.,Ferreira, Sandra S.,Trant, John F.,Ben, Robert N.
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- Regio- and stereo-selective synthesis of peracetylated carbohydrate esters of aromatic fatty acid using p-toluenesulfonic acid as catalyst
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This paper describes an efficient synthesis of carbohydrate fatty acid esters based on a highly stereo- and regio-selective esterification. The suitably protected glycosyl was esterified with stearic acid to give mainly the β-anomer in good yield using p-toluenesulfonic acid as catalyst. The structures of these compounds were fully confirmed by 1H, 13C NMR, mass spectra and HRMS. The suitably protected glycosyl was esterified with stearic acid to give mainly the β-anomer in good yield using p-toluenesulfonic acid as catalyst. The structures of these compounds were fully confirmed by 1H, 13C NMR, mass spectra and HRMS. Copyright
- Zhu, Zhenyuan,Li, Shengfeng,Liu, Rongqiang,Yuan, Jing,Wang, Haibiao,Zhang, Yongmin,Liu, Yang
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- SYNTHESIS OF OLIGOSACCHARIDES BY USING LEVULINIC ESTER AS AN HYDROXYL PROTECTING GROUP
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The fast, selective and mild removal of levulinyl groups with hydrazine from galactose, wich also carries hydroxyl functions protected with acetyl groups, enables, under Koenigs-Knorr conditions, the synthesis of a trimer containing β-linked galactoses.
- Koeners, H. J.,Verhoeven, J.,Boom, J. H.
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- Selective 1-O-deacetylation of carbohydrates using polymer-bound benzylamine
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A new method for highly effective and selective 1-O-deacetylation o f peracetylated carbohydrates using polymer-bound amines is presented. Georg Thieme Verlag Stuttgart.
- Johnsson, Richard,Ellervik, Ulf
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- Chemoenzymatic synthesis of a glycolipid library and elucidation of the antigenic epitope for construction of a vaccine against lyme disease
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Lyme disease (LD) is the most common tick-borne disease in Europe, North America, and Asia. The etiologic agents of LD are spirochetes of the group Borrelia burgdorferi sensu lato, which possess a lipid content of 25-30% of the dry weight. The major glycolipid cholesteryl 6-O-acyl-ss-D- galactopyranoside (ACGal), present in B. burgdorferi sensu stricto, B. afzelii, and B. garinii, is a specific and highly prevalent antigen frequently recognized by antibodies in late-stage LD. Here we report a convenient route for the chemical synthesis of ACGal by employing a combination of chemical synthesis steps with enzymatic transformations. This synthesized molecule was compared with bacterial extracts by immunoblots with patient sera, confirming the preserved antigenicity. Next, a glycolipid library derived from the native molecules with variations in the fatty acyl moiety and derivatives in which the cholesterol has been replaced was designed and synthesized. The chemical structures were confirmed by lD and 2D NMR spectroscopy and mass spectrometry. The native and synthetic glycolipids were utilized in immunoblots to determine the epitope recognized by antibodies in patient sera. By this method we could demonstrate that galactose, cholesterol, and a fatty acid with a minimal chain length of four carbon atoms comprises the essential structure for recognition by antibodies. Finally, this finding allowed the synthesis of a functionalized ACGal with an ω-mercapto group at the fatty acid and a facile protection and deprotection strategy. This antigenic hapten can be conjugated to a carrier protein to effect immunization against Lyme disease.
- Stuebs, Gunthard,Rupp, Bernd,Schumann, Ralf R.,Schroeder, Nicolas W. J.,Rademann, Joerg
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- Regioselective anomeric deacetylation of peracetylated glycopyranoses
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A simple and mild method for regioselective anomeric deacetylation of peracetylated glycopyranoses using copper(II) acetate dihydrate and methanol/water (9:1) is described.
- Bhaumik, Kankan,Salgaonkar, Paresh D.,Akamanchi
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- Incorporation of 'click' chemistry glycomimetics dramatically alters triple-helix stability in an adiponectin model peptide
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Adiponectin (Adpn) has been shown to be a possible therapeutic for Type II diabetes, however the production of a therapeutic version of Adpn has proved to be challenging. Biological studies have highlighted the importance of the glycosylated lysine residues for the formation of bioactive high molecular weight oligomers of Adpn. Through the use of 'click' glycopeptide mimetics, we investigated the role of glycosylated lysine and serine residues for the formation of triple helical structures of the collagenous domain of Adpn, in the context of a collagen model peptide scaffold. The physical properties of the unglycosylated lysine and serine peptides are compared with their glycosylated analogues. Our results highlight the crucial role of lysine residues for formation of the triple helical structure of Adpn, possibly due to the extension of both intra- and interstrand hydrogen bonding networks. Strikingly, we observed a significant decrease in thermal stability upon incorporation of triazole-linked analogues of glycosylated lysine residues into the adiponectin collageneous domain, indicating possible uses of 'click' glycomimetics for bioengineering applications.
- Lutteroth, Katherine R.,Harris, Paul W.R.,Wright, Tom H.,Kaur, Harveen,Sparrow, Kevin,Yang, Sung-Hyun,Cooper, Garth J.S.,Brimble, Margaret A.
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- Esterase catalyzed regioselective hydrolyses of acetylated monosaccharides
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Deacylations of fully acylated D-glucopyranoses, methyl D-glucopyranosides, 2-acetamido-2-deoxy-D-glucopyranoses glucopyranoses and methyl 2-acetamido-2-deoxy-D-glucopyranosides catalyzed by rabbit serum or the esterase isolated from rabbit serum were investigated. Depending on the structure of the acyl protecting group a high degree of regioselectivity is observed. Products of enzymic hydrolysis followed by intramolecular migrations of acetyl groups are also described.
- Tomic, Srdanka,Ljevakovic, Durjica,Tomasic, Jelka
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- Synthesis of 13C-labelled sulfated N-acetyl-d-lactosamines to aid in the diagnosis of mucopolysaccharidosis diseases
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Morquio A syndrome is an autosomal mucopolysaccharide storage disorder that leads to accumulation of keratan sulfate. Diagnosis of this disease can be aided by measuring the levels of keratan sulfate in the urine. This requires the liquid chromatography tandem mass spectrometry (LCMS/MS) measurement of sulfated N-acetyl-d-lactosamines in the urine after cleavage of the keratan sulfate with keratanase II. Quantification requires isotopically-labelled internal standards. The synthesis of these 13C6-labelled standards from 13C6-galactose and N-acetylglucosamine is described. The required protected disaccharide is prepared utilising a regioselective, high yielding β-galactosylation of a partially protected glucosamine acceptor and an inverse addition protocol. Subsequent synthesis of the 13C6-labelled mono and disulfated N-acetyllactosamines was achieved in five and eight steps, respectively, from this intermediate to provide internal standards for the LCMS/MS quantification of keratan sulfate in urine.
- Cameron, Scott A.,Zubkova, Olga V.,Toms, Steven,Furneaux, Richard H.,Rendle, Phillip M.
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- New glycosidase activated nitric oxide donors: Glycose and 3-morphorlinosydnonimine conjugates
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(Chemical Equation Presented) To achieve site specific delivery of nitric oxide (NO), a new class of glycosidase activated NO donors has been developed. Glucose, galactose, and N-acetylneuraminic acid were covalently coupled to 3-morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a carbamate linkage at the anomeric position. The β-glycosides were successfully prepared for these conjugates, while the α-glycosidic compounds were very unstable. The new stable sugar-NO conjugates could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in biomedical research.
- Cai, T. Bill,Lu, Dongning,Tang, Xiaoping,Zhang, Yalong,Landerholm, Megan,Wang, Peng George
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- Synthesis of (-)-epigallocatechin-3-gallate derivative containing a triazole ring and combined with cisplatin/paclitaxel inhibits NSCLC cancer cells by decreasing phosphorylation of the EGFR
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Non-small-cell lung cancer is one of the principal causes of cancer-related death around the world. Chemotherapy is commonly used to treat wild type of epidermal growth factor receptor non-small-cell lung cancer. (-)-Epigallocatechin-3-gallate is the most abundant and active catechin. However, (-)-epigallocatechin-3-gallate has limited clinical application due to its poor stability and absorption. Herein, we report that a glycosylated azide undergoes a click reaction with the terminal alkyne of (-)-epigallocatechin-3-gallate to yield a triazole-linked glucose-(-)-epigallocatechin-3-gallate derivative and have evaluated its in vitro anticancer activity against human non-small-cell lung cancer cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The product inhibits human non-small-cell lung cancer cell lines with wild type of epidermal growth factor receptor and in combination with cisplatin/paclitaxel results in more pronounced proliferation inhibition than when used alone. Stability investigations indicates that the conjugated glucose residue can improve the stability of the (-)-epigallocatechin-3-gallate scaffold. Our studies suggest that the combination of the glucose-(-)-epigallocatechin-3-gallate derivative and chemotherapeutic drugs may provide a novel strategy for the treatment of non-small-cell lung cancer.
- Zi, Cheng-Ting,Sun, Pei-Yuan,Zhang, Ning,Tang, Han,Yang, Hao-Nang,Wang, Qi,Wang, Yu-Na,Wang, Jing,Wang, Xuan-Jun,Sheng, Jun
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- Synthesis of five-membered heterocycles by indirect electrochemical approach in Green media
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Radical cyclization continues to be a central methodology for the preparation of natural products containing heterocyclic rings. Hence, some electrochemical results obtained by cyclic voltammetry and controlled-potential electrolysis in the study of electroreductive intramolecular cyclization of ethyl (2S, 3R)-2-bromo-3-propargyloxy-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy) propanoate (1a), 2-bromo-3-allyloxy-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)propanoate (1b), 2-bromo-[1-(prop-2-yn-1-yloxy)propyl]benzene (1c) and [1-bromo-2-methoxy-2-(prop-2′-yn-1-yloxy)ethyl]benzene (1d) promoted by (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane)nickel(I), [Ni(tmc)]+, electrogenerated at glassy carbon cathodes in ethanol and ethanol:water mixtures containing tetraalkylammonium salts, are presented. During controlled-potential electrolyses of solutions containing [Ni(tmc)]2+ and bromoalkoxylated compounds (1) catalytic reduction of the latter proceeds via one-electron cleavage of the carbon-bromine bond to form a radical intermediate that undergoes cyclization to afford the substituted tetrahydrofurans.
- Dures,Lombard,Pereira,Esteves,Medeiros
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- Studies on the stereoselective synthesis and immunosuppressive activity of dihydroartemisinin-O-glycoside derivatives
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Eight new dihydroartemisinin-O-glycosides were synthesized with their relative configurations were determined based on NMR spectrum. In vitro immunosuppressive assay showed that 10α-dihydroartemisinin-β-O-D-mannoside (19a) demonstrate 88percent inhibition towards T cells proliferation and 98percent reduction in IFN-γ levels in cell media. These results suggest that dihydroartemisinin-O-glycoside as a potential lead for further in vivo evaluation.
- Bian, Hongzhu,Dong, Xun,Shen, Zhengwu,Xu, Wei,Yu, Jingfeng,Yu, Yu,Zhang, Jinghua,Zou, Xiaosu
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- Regio- and stereo-selective bromo(alkoxylation)s of (E)-α-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxymethylene) carbonyl compounds. A route to near-stereopure α-bromo α-dioxymethyl carbonyl compounds
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(E)-4-Methoxymethoxy-3-methylbut-3-en-2-one 17b reacts with NBS in propan-1-ol in a highly regio- and anti-stereo-selective manner to give (3R*-,4R*)-3-bromo-4-methoxymethoxy-3-methyl-4-propoxybutan-2-one 18. Compound 10, a relative of the butenone 17b in which the methoxymethyl group is replaced by the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit, undergoes an analogous bromo(propoxylation) reaction with reasonable facial selectivity to give an 86:14 mixture of (3R,4R)-3-bromo-3-methyl-4-propoxy-4-(2′,3′,4′,6′-tetra- O-acetyl-β-D-glucopyranosyloxy)butan-2-one 11c and its (3S,4S)-diastereomer 12c. The major bromo(propoxy) derivative, isolable in 57% yield by fractional crystallisation, is assigned the stereostructure 11c by single-crystal X-ray crystallographic analysis. Other primary alcohols and methanol participate in the reaction of compound 10 with NBS, leading predominantly (with selectivities ranging from 75:25 to 89:11) to bromo(alkoxy) products of type 11 which are usually separable from their diastereomers of type 12 by fractional crystallisation (in yields ranging from 41 to 64%). A model to account for the role of the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit in the stereoinduction process is proposed. Related bromo(propoxylation)s are observed with the vinylogous esters 24, 25a and 25b, leading to the isolation of the major products, 28, 30a and 30b (in yields ranging from 39 to 55%), and with the vinylogous carbonates 32a, 32c, 37a and 37b, providing access to the major products 33a, 33c, 38a and 38b (in yields ranging from 52 to 73%). In the presence of trifiuoroacetic acid and ethane-1,2-diol, the bromo(propoxy) derivatives 11c, 28, 30b and 33c undergo transacetalisation to give the ethylene glycol acetals 40a, 40b, 41 and 40c with ees of 94-98%, in yields ranging from 56 to 67%. The Royal Society of Chemistry 2000.
- Idris, M. Sum,Larsen, David S.,Pritchard, Robin G.,Schofield, Anthony,Stoodley, Richard J.,Tiffin, Peter D.
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- An alternative approach for the synthesis of sulfoquinovosyldiacylglycerol
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Sulfoquinovosyldiacylglycerol (SQDG) is a glycolipid ubiquitously found in photosyn-thetically active organisms. It has attracted much attention in recent years due to its biological ac-tivities. Similarly, the increasing demand for vegan and functional foods has led to a growing interest in micronutrients such as sulfolipids and their physiological influence on human health. To study this influence, reference materials are needed for developing new analytical methods and providing enough material for model studies on the biological activity. However, the availability of these materials is limited by the difficulty to isolate and purify sulfolipids from natural sources and the unavailability of chemical standards on the market. Consequently, an alternative synthetic route for the comprehensive preparation of sulfolipids was established. Here, the synthesis of a sulfolipid with two identical saturated fatty acids is described exemplarily. The method opens possibilities for the preparation of a diverse range of interesting derivatives with different saturated and unsatu-rated fatty acids.
- Domey, Hendrik,Fischer, Judith,Rohn, Sascha,Sitz, Tobias
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- Streamlining routine organic chemistry reactions by the employment of high shear mixers
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Some organic reactions involve long reaction times and high energy consumption. Herein, an improved method to accelerate the reactions by the employment of a high shear mixer is described. The produced emulsion minimizes the mass transfer resistance and reaction times, improves yields, and saves energy, in agreement with the Green Chemistry principles.
- Zeferino-Díaz, Reyna,Hilario-Martínez, J. Ciciolil,Sánchez-Cantú, Manuel,Fernández-Herrera, María A.,Sandoval-Ramirez, Jesus
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- Regioselective hydrolysis of peracetylated α-D-glucopyranose catalyzed by immobilized lipases in aqueous medium. A facile preparation of useful intermediates for oligosaccharide synthesis
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Penta-O-acetyl-α-D-Glucopyranose was selectively deacetylated in aqueous media by lipases from Candida cilindracea (CCL) adsorbed on octyl- agarose support. Enzymatic hydrolyses was regioselective at the 4-position under neutral pH and towards the 6 position under acidic conditions. This enzymatic approach allows the one step synthesis of 1,2,3,6-tetra-O-acetyl- α-D-glucopyranoses 1, a useful intermediate in oligosaccharide synthesis.
- Bastida, Agatha,Fernandez-Lafuente, Roberto,Fernandez-Lorente, Gloria,Guisan, Jose M.,Pagani, Giuseppe,Terreni, Marco
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- Efficient synthesis of hydrophilic phosphodiester derivatives of lipophilic alcohols via the glycosyl hydrogenphosphonate method
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The preparation of five peracetylated a-glycosyl-H-phosphonates and their use in the straightforward preparation of phosphodiesters derivatives of 25-hydroxycholesterol is described. Examples of the extension of this process to other lipophilic alcohols are presented.
- Knerr, Laurent,Pannecoucke, Xavier,Luu, Bang
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- cycloSaligenyl-mannose-1-monophosphates as a new strategy in CDG-Ia therapy: Hydrolysis, mechanistic insights and biological activity
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Phosphomannomutase 2 (PMM-2) deficiency leads to an inefficient intracellular formation of mannose-1-phosphate (1), which causes an inherited metabolic disease with multisystemic abnormalities (Congenital Disorder of Glycosylation type Ia, CDG-Ia). In order to circumvent this metabolic deficiency, the cycloSal approach was applied for the intracellular delivery of mannose-1-monophosphate (1). cycloSaligenyl-pyranose-1-monophosphates 6-11 were obtained by a phosphitylation/oxidation procedure starting from appropriately protected D-pyranoses. The chemical hydrolysis data and the involved hydrolysis mechanisms of cyclosaligenyl-mannose-1-monophosphates 6-9 and their epimeric glucose analogues 10, 11 are reported. Furthermore, the biological activity of cycloSal-mannose-1-phosphates 6-9 was tested in vitro in PMM-2-deficient fibroblasts. 3-Methyl-cycloSal-2,3,4,6-tetra-O-acetyl-α-D-mannopyranose-1- monophosphate (8) showed a total correction of the phenotype, thus proving the delivery of mannose-1-phosphate. This may offer a suitable possibility for a therapy of CDG-Ia. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Muus, Ulrike,Kranz, Christian,Marquardt, Thorsten,Meier, Chris
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- Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis
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Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
- Li, Zhihao,Bavaro, Teodora,Tengattini, Sara,Bernardini, Roberta,Mattei, Maurizio,Annunziata, Francesca,Cole, Richard B.,Zheng, Changping,Sollogoub, Matthieu,Tamborini, Lucia,Terreni, Marco,Zhang, Yongmin
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- Easy access to glycosyl phosphorothioates with microwaves technique
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A simple, efficient, and general method for the synthesis of glycosyl phosphorothioate through a one-pot reaction of glycosyl bromide with diethyl phosphite, ammonium acetate, and sulphur in the presence of alumina under solvent-free conditions using microwave irradiation has been developed. Copyright Taylor & Francis Group, LLC.
- Cipolla, Laura,Redaelli, Cristina,Faria, Iris,Nicotra, Francesco
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- Joining hydroxyazobenzene and mannose under mitsunobu conditions
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The Mitsunobu reaction has been revisited to join hydroxyazobenzene and mannose derivatives to supply photoswitchable glycoconjugates. These are suited to modulating and controlling carbohydrate-lectin interactions, as well as to switching bacterial adhesion to surfaces. Employing hydroxyazobenzene in a Mitsunobu protocol, free mannose led to a mixture of azobenzene pyranosides and furanosides. Protected reducing mannose derivatives can give good yields of azobenzene β-D-mannopyranoside, and unprotected alkyl α-D-mannosides can be converted to 6-O-azobenzene-modified glycosides in a single step. Thus, valuable "sweet switches" can be obtained under Mitsunobu conditions, requiring a minimum (or no) protecting group chemistry.
- Hain, Julia,Chandrasekaran, Vijayanand,Lindhorst, Thisbe K.
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- NIS/TFA: a general method for hydrolyzing thioglycosides
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A variety of thioglycosides are chemoselectively hydrolyzed to the corresponding 1-hydroxy glycosides using equimolar amounts of NIS/TFA as promoter systems.
- Dinkelaar, Jasper,Witte, Martin D.,van den Bos, Leendert J.,Overkleeft, Herman S.,van der Marel, Gijsbert A.
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- Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogues1-4
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A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds were achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10 °C to give a nearly quantitative yield of 10-O- (trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1- hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross- resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day x 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day x 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day x 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.
- Lin,Li,Andersen,Klayman
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- Synthetic glycosides containing two isosteviol fragments functionalized with D-glucopyranose
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The synthesis of isosteviol (16-oxo-ent-beyeran-19-oic acid) glycosides in which two isosteviol fragments functionalized with tetra-O-acetyl-D- glucopyranose are linked through a diester spacer is described for the first time.
- Garifullin,Sharipova,Strobykina, I. Yu.,Babaev,Kataev
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- Oxidative deprotection of allyl glycosides
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Allyl glycosides can be deprotected under the condition of the Kharasch- Sosnovsky reaction and by photoinduced reaction with di-(t)butylperoxide in the presence of bromotrichloromethane.
- Kraehmer, Ralf,Hennig, Lothar,Findeisen, Matthias,Mueller, Dietrich,Welzel, Peter
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- Synthesis of harounoside, a naturally occurring pentalongin hydroquinone bisglucoside
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The recently isolated natural product harounoside, namely 5,10-dihydroxy-2H-naphtho[2,3-c]pyran-β-D-bisglucopyranoside, was conveniently synthesized for the first time from pentalongin in 84% yield over three steps. Georg Thieme Verlag Stuttgart.
- Van Nguyen, Tuyen,Claessens, Sven,Habonimana, Pascal,Tehrani, Kourosch Abbaspour,Van Puyvelde, Luc,De Kimpe, Norbert
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- Design, synthesis, and cytotoxicity evaluation of threonine-based galactoceramide with aromatic groups and various fatty-acyl side chains
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Abstract: In galactoceramides, presence of fatty-acyl group on amide moiety or phytosphingosine group is some of the important features that influence the cytotoxicity. Continuous efforts are in progress to modify the fatty-acid moiety and phytosphingosine group present on the galactoceramides to enhance the cytotoxic potential of these compounds. Hence, in the present study, threonine-based β-galactoceramide and its derivatives were prepared by modifying the fatty-acyl group on amide moiety with different fatty-acyl moieties and aromatic acids employing trichloroacetimidate methodology. The structurally related threonine-based ceramide part was synthesized in multi-step process using different reagents. The ceramide part was glycosylated with galactose using trichloroacetimidate as donor. Further, all the synthesized compounds were evaluated for in vitro cytotoxicity against three cancer cell lines and one normal cell line and all the compounds exhibited good to moderate cytotoxicity against all the tested cancer cell lines. In aromatic derivatives, the compound 8i exhibited promising activity against MCF7, A549 and HeLa cancer cell lines with IC50 values of 14.08, 14.78, and 16.70 μM, respectively. In fatty-acid derivatives, two compounds exhibited promising activity, i.e., compound 8m against HeLa with IC50 value 16.34 μM and compound 8n against MCF7 with IC50 value 18.05 μM. Based on structure–activity relationship, aromatic acid derivatives exhibited potential activity as compared to fatty-acid derivatives. Further, the influence of some of the key factors such as spacer chain length between aromatic residue and amide functional group, methoxy substituents on aryl group, terminal unsaturation of fatty acid and branching chain effect on the cytotoxicity are discussed.
- Vudhgiri, Srikanth,Routhu, Sunitha Rani,Kumar, C. Ganesh,Prasad,Reddy Jala, Ram Chandra
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- Stereospecific synthesis of retinoic acid glucoconjugates, as pseudo- substrates of epidermal β-glucocerebrosidase
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The synthesis of glucocerebrosides (precursors of skin lipids) analogues bearing the bioactive compound retinoic acid is described; the two diastereoisomeric gluco-conjugates glucose-glycerol-retinoic acid are pseudo- subtrates for the title enzyme.
- Redoules, Daniel,Perie, Jacques
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- BORON TRIFLUORIDE ETHERATE AS AN EFFECTIVE REAGENT FOR THE STEREOSELECTIVE ONE-POT CONVERSION OF ACETYLATED 2-TRIMETHYLSILYLETHYL GLYCOSIDES INTO SUGAR 1,2-TRANS-ACETATES.
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Treatement of 2-trimethylsilylethyl glycosides with boron trifluoride etherate in the presence of acetic anhydride gave the corresponding sugar acetate in >90percent isolated yield and with a 1,2-trans:cis ratio of >20:1.The sugar with a free anomeric hydroxyl group was obtained when acetic anhydride was omitted.
- Jansson, Karl,Frejd, Torbjoern,Kihlberg, Jan,Magnusson, Goeran
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- O-(3-Butenyl), a stable blocking group removable by ozonolysis
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Among the many blocking groups used in carbohydrate chemistry, only a few can be removed under very mild and neutral conditions, while resisting the reagents generally applied in chemical reactions. We demonstrate here the utility of the O-(3-butenyl) group for differential protection in carbohydrates. The 3-butenyl group is readily attached to the anomeric oxygen atom of any reducing mono- or oligo-saccharide, using either the Koenigs-Knorr or Fischer type of reaction with 3-buten-1-ol as the aglyconic alcohol.
- Bayle,Defaye,Horton,Lehman,Scheuring
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- Synthesis of malformin-A1, C, a glycan, and an aglycon analog: Potential scaffolds for targeted cancer therapy
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Improvement in therapeutic efficacy while reducing chemotherapeutic side effects remains a vital objective in synthetic design for cancer treatment. In keeping with the ethos of therapeutic development and inspired by the Warburg effect for augmenting biological activities of the malformin family of cyclic-peptide natural products, specifically anti-tumor activity, a β-glucoside of malformin C has been designed and synthesized utilizing precise glycosylation and solution phase peptide synthesis. We optimized several glycosylation procedures utilizing different donors and acceptors. The overarching goal of this study was to ensure a targeted delivery of a glyco-malformin C analog through the coupling of D-glucose moiety; selective transport via glucose transporters (GLUTs) into tumor cells, followed by hydrolysis in the tumor microenvironment releasing the active malformin C a glycon analog. Furthermore, total synthesis of malformin C was carried out with overall improved strategies avoiding unwanted side reactions thus increasing easier purification. We also report on an improved solid phase peptide synthesis protocol for malformin A1.
- Andreana, Peter R.,Hossain, Farzana,Nishat, Sharmeen
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- Total synthesis of three natural phenethyl glycosides
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Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.
- Dong, Hong-Bo,Meng, Jian,Yao, Zhong-Quan,Luo, Hong-Bing,Zhang, Jing-Xia,Du, Wei-Hong,Tang, Ke-Hui,Cao, Sheng-Hua
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p. 284 - 293
(2020/03/03)
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- First total syntheses of two natural glycosides
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Isosyringinoside (1) and 3-(O-β-D-glucopyranosyl)-α-(O-β-D-glucopyranosyl)-4-hydroxy phenylethanol (2), the natural bioactive compounds contained unique structures, were first totally synthesized using easily available materials in short convenient routes with overall yields of 20.2% and 27.0%, respectively. An efficient total synthesis of 1 was developed in six steps, which contained two key steps of highly regioselective glycosylation without any selective protection steps. The seven-step synthesis of 2 involved two steps of regioselective glycosylations using BF3–O(C2H5)2 and TMSOTf as catalysts, respectively.
- Dong, Hongbo,Du, Weihong,Yao, Zhongquan,Wu, Min,Luo, Hongbing,He, Yujiao,Cao, Shenghua
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supporting information
(2020/12/02)
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- Scalable Total Synthesis of Piceatannol-3′-O-β-d-glucopyranoside and the 4′-Methoxy Congener Thereof: An Early Stage Glycosylation Strategy
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Scalable syntheses of piceatannol-3'-O-β-D-glucopyranoside and the 4'-methoxy congener thereof were achieved. This route features an early implemented Fischer-like glycosylation reaction, a regioselective iodination of phenolic glycoside under strongly acidic conditions, a highly telescoped route to access the styrene derivative, and a key Mizoroki.Heck reaction to render the desired coupled products in high overall yield.
- Chen, Lei,Li, Jianfeng,Wang, Xiaoting,Zhang, Rong-Ping
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- 3'-KETOGLYCOSIDE COMPOUND FOR THE SLOW RELEASE OF A VOLATILE ALCOHOL
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The present invention relates to a 3'-ketoglycoside compound defined by formula (I) and its use for controlled release of alcohols, in particular alcohols showing an insect repellent effect. It relates also to a process for preparing the 3'-ketoglycoside compound of formula (I). It further relates to a composition comprising a 3'- ketoglycoside compound of formula (I). It relates also to the use of a 3'-ketoglycoside compound of formula (I) for the controlled release of alcohols. It related also to a method of use of such composition.
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Page/Page column 35
(2021/08/20)
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- Mannose-modified azide exosome and application thereof
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The invention belongs to the field of biological medicine, and particularly relates to a mannose-modified azide exosome and an application thereof. The mannose-modified azide exosome is prepared through metabolic labeling and click chemistry reaction; the advantages of the surface-functionalized azide exosome targeting macrophages are determined through a flow cytometry on the cellular level, and in-vitro pharmacological experiments prove that the mannose-modified azide exosome has the advantage of treating infectious diseases after being loaded with drugs. According to the surface-functionalized azide exosome provided by the invention, the targeting property of the exosome as a drug carrier can be greatly improved, and the effect of the surface-functionalized azide exosome in treating refractory infectious related diseases is improved.
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Paragraph 0056; 0062; 0065
(2021/06/23)
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- Preparation and formulation optimization of methotrexate-loaded human serum albumin nanoparticles modified by mannose
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Background: Methotrexate (MTX) is the representative drug among the dis-ease-modifying anti-rheumatic drugs. However, the conventional treatment with MTX showed many limitations and side effects. Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which are referred to as MTX-M-NPs. Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by the method of central composite design (CCD), with the drug lipid ra-tio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. The response of different formulations was calculated, and the response surface diagram, con-tour diagram, and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neu-trophils was studied through confocal laser detection. Further, MTX-M-NPs were subject-ed to assessment of the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats. Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized for-mula, MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could pro-long the in vivo circulation time of MTX. Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.
- Chen, Zhenyu,Lin, Yan,Liu, Zhongbing,Luo, Zhongling,Lyu, Jiayao,Wang, Jianxin,Wei, Jun,Zhong, Zhirong
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p. 5016 - 5029
(2021/08/17)
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- Fluorinated rhamnosides inhibit cellular fucosylation
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The sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.
- Boltje, Thomas J.,Eerden, Nienke,Lefeber, Dirk J.,Merx, Jona,Noga, Marek J.,Pijnenborg, Johan F. A.,Rossing, Emiel,Titulaer, Willem H. C.,Veizaj, Raisa,White, Paul B.
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- Self-Promoted Glycosylation for the Synthesis of β-N-Glycosyl Sulfonyl Amides
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N-Glycosyl N-sulfonyl amides have been synthesized by a self-promoted glycosylation, i. e. without any catalysts, promotors or additives. When the reactions were carried out at lower temperatures a mixture of N- and O-glycosides were observed, where the latter rearranged to give the β-N-glycosides at elevated temperatures. By this method sulfonylated asparagine derivatives can be selectively β-glycosylated in high yields by trichloroacetimidate glycosyl donors of different reactivity including protected glucosamine derivatives. The chemoselectivity in the glycosylations as well as the rearrangements from O-glycosides to β-N-glycosides gives information of the glycosylation mechanism. This method gives access to glycosyl sulfonyl amides under mild conditions.
- Ma?a, Patrycja,Pedersen, Christian Marcus
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supporting information
p. 5685 - 5689
(2021/08/30)
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- Synthesis of Glycosyl Fluorides by Photochemical Fluorination with Sulfur(VI) Hexafluoride
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This study describes a new convenient method for the photocatalytic generation of glycosyl fluorides using sulfur(VI) hexafluoride as an inexpensive and safe fluorinating agent and 4,4′-dimethoxybenzophenone as a readily available organic photocatalyst. This mild method was employed to generate 16 different glycosyl fluorides, including the substrates with acid and base labile functionalities, in yields of 43%-97%, and it was applied in continuous flow to accomplish fluorination on an 7.7 g scale and 93% yield.
- Bannykh, Anton,Khomutnyk, Yaroslav,Kim, Sungjin,Nagorny, Pavel
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supporting information
p. 190 - 194
(2021/01/13)
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- Rh2(II)-Catalyzed intermolecular N-Aryl aziridination of olefins using nonactivated N atom precursors
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The development of the first intermolecular Rh2(II)-catalyzed aziridination of olefins using anilines as nonactivated N atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. This reaction requires the transfer of an N-aryl nitrene fragment from the iminoiodinane intermediate to a Rh2(II) carboxylate catalyst; in the absence of a catalyst only diaryldiazene formation was observed. This N-aryl aziridination is general and can be successfully realized by using as little as 1 equiv of the olefin. Di-, tri-, and tetrasubstituted cyclic or acylic olefins can be employed as substrates, and a range of aniline and heteroarylamine N atom precursors are tolerated. The Rh2(II)-catalyzed N atom transfer to the olefin is stereospecific as well as chemo- and diastereoselective to produce the N-aryl aziridine as the only amination product. Because the chemistry of nonactivated N-aryl aziridines is underexplored, the reactivity of N-aryl aziridines was explored toward a range of nucleophiles to stereoselectively access privileged 1,2-stereodiads unavailable from epoxides, and removal of the N-2,4-dinitrophenyl group was demonstrated to show that functionalized primary amines can be constructed.
- Deng, Tianning,Mazumdar, Wrickban,Yoshinaga, Yuki,Patel, Pooja B.,Malo, Dana,Malo, Tala,Wink, Donald J.,Driver, Tom G.
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supporting information
p. 19149 - 19159
(2021/11/23)
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- Eradicating intracellular MRSA via targeted delivery of lysostaphin and vancomycin with mannose-modified exosomes
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Intracellular methicillin-resistant Staphylococcus aureus (MRSA) is extremely difficult to remove by common antibiotics, leading to infection recurrence and resistance. Herein we report a novel exosome-based antibiotic delivery platform for eradicating intracellular MRSA, where mannosylated exosome (MExos) is employed as the drug carrier and preferentially taken up by macrophages, delivering lysostaphin (MExoL) and vancomycin (MExoV) to intracellular pathogens. Combination of MExoL and MExoV eradicated intracellular quiescent MRSA. Moreover, MExos rapidly accumulated in mouse liver and spleen, the target organs of intracellular MRSA, after intravenous (IV) administration. Thus, the MExos antibiotic delivery platform is a promising strategy for combating intracellular infection.
- Yang, Xiaohong,Xie, Beibei,Peng, Haibo,Shi, Gongming,Sreenivas, Banne,Guo, Jian,Wang, Chenhui,He, Yun
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p. 454 - 467
(2020/12/25)
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- A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells
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Eight mono- or disaccharide analogues derived from BLM disaccharide, along with the corresponding carbohydate-dye conjugates have been designed and synthesized in this study, aiming at exploring the effect of a gulose residue on the cellular binding/uptake of BLM disaccharide and it possible uptake mechanism. Our evidence is presented indicating that, for the cellular binding/uptake of BLM disaccharide, a gulose residue is an essential subunit but unrelated to its chemical nature. Interestingly, D-gulose-dye conjugate is able to selectively target A549 cancer cells, but L-gulose-dye conjugate fails. Further uptake mechanism studies demonstrate D-gulose-dye derivatives similar to BLM disaccharide-dye ones behave in a temperature- and ATP-dependent manner, and are partly directed by the GLUT1 receptor. Moreover, D-gulose modifying gemcitabine 53a exhibits more potent antitumor activity compared to derivatives 53b-c in which gemcitabine is decorated with other monosaccharides. Taken together, the monosacharide D-gulose conjugate offers a new strategy for solving cytotoxic drugs via the increased tumor targeting in the therapy of lung cancer.
- Cao, Yongjun,Chen, Wenming,Huang, Weiping,Li, Houkai,Liao, Guohao,Qi, Dongxia,Wang, Meizhu,Wang, Xiaoyang,Ye, Wenchong,Zhou, Cui,Zhou, Wen
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supporting information
(2021/10/07)
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- Nanoparticles to Study Lectins in Caenorhabditis elegans: Multivalent Galactose β1-4 Fucose-Functionalized Dendrimers Provide Protection from Oxidative Stress
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Galectins are galactoside-binding lectins that are functional dimers or higher-order oligomers. Multivalent binding has been shown to augment the relatively low affinity of the galectins for their galactoside-binding partners, enabling the galectins to pl
- Vankoten, Harrison W.,Moore, Rebecca S.,Cloninger, Mary J.
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p. 4720 - 4729
(2021/11/17)
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- Preparation method of tetraacetyl glucose
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The invention belongs to the technical field of organic synthesis and relates to a preparation method of tetraacetylglucose. The invention provides a preparation method of tetraacetylglucose. According to the preparation method, bromo-tetraacetylglucose is adopted as a reaction substrate, a reaction is performed in a reaction system containing water, an organic solvent, a phase transfer catalyst and inorganic base under the action of an organic base catalyst to generate tetraacetylglucose; and the organic base catalyst is selected from any one component or a combination of components selected from triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 2, 6-dimethylpyridine, 2, 4, 6-trimethylpyridine, 4-pyrrolidinyl pyridine, 4-morpholinyl pyridine and 4-dimethylamino pyridine.
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Paragraph 0034-0050
(2021/04/07)
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- Carbonyl compound containing amino acid connecting chain or pharmaceutically acceptable salt thereof, and preparation method and application of carbonyl compound
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The invention provides a carbonyl compound containing an amino acid connecting chain or a pharmaceutically acceptable salt thereof as well as a preparation method and application of the carbonyl compound, and belongs to the technical field of anti-AIDS medicines. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the invention has a structure shown as formula I in the specification. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the inventionhas obvious activity of inhibiting HIV protease; the obvious inhibition activity is realized on the DRV drug-resistant strain; toxicity research shows that the compound is low in toxicity and has gooddruggability; the inhibitory activity on HIV-1 protease is 286-1052 times of the inhibitory activity of a positive control drug DRV on HIV-1 protease; the inhibitory activity on a DRV drug-resistantstrain and the inhibitory activity on a wild HIV-1 drug-resistant strain are only reduced by 1.10-3.23 times, and the compound has a good application prospect as an anti-AIDS drug.
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Paragraph 0215; 0227-0229
(2020/06/16)
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- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
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In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
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- Tea leaf perfumery precursor glucoside and synthesizing method thereof
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The invention relates to a tea leaf perfumery precursor glucoside and a synthesizing method thereof. The synthesizing method comprises the following steps of synthesizing ten glucosides including aromatic alcohol ( alkanol )-beta -D-glucosides and aromatic alcohol (alkanol )-beta -D-primrose indicans. The synthesizing method disclosed by the invention is a glucoside synthesizing method which is good in selectivity, high in production rate and low in cost.
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Paragraph 0044-0046; 0050-0051
(2020/07/02)
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- Synthesis of photolabile group protected anomeric acetals and its application in carbohydrate synthesis with the assistance of continuous flow photo-reactor
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Selective deprotection of photolabile anomeric 2-nitrobenzyl acetals was achieved using continuous flow photo-reactor (UV radiation at 355 nm) in methanol-water. Various protecting groups such as acetyl, benzyl, benzoyl, benzylidine, TBS, etc. were found to be highly stable during the photolysis.
- Tiwari, Varsha,Badavath, Vishnu Nayak,Singh, Adesh Kumar,Kandasamy, Jeyakumar
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p. 227 - 236
(2020/03/18)
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- Total Synthesis of Tri-, Hexa- and Heptasaccharidic Substructures of the O-Polysaccharide of Providencia rustigianii O34
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A general and efficient strategy for synthesis of tri-, hexa- and heptasaccharidic substructures of the lipopolysaccharide of Providencia rustigianii O34 is described. For the heptasaccharide seven different building blocks were employed. Special features of the structures are an α-linked galactosamine and the two embedded α-fucose units, which are either branched at positions-3 and -4 or further linked at their 2-position. Convergent strategies focused on [4+3], [3+4], and [4+2+1] couplings. Whereas the [4+3] and [3+4] coupling strategies failed the [4+2+1] strategy was successful. As monosaccharidic building blocks trichloroacetimidates and phosphates were employed. Global deprotection of the fully protected structures was achieved by Birch reaction.
- Ahadi, Somayeh,Awan, Shahid I.,Werz, Daniel B.
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supporting information
(2020/05/04)
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- Dehydrative Glycosylation Enabled by a Comproportionation Reaction of 2-Aryl-1,3-dithiane 1-Oxide?
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A new dehydrative glycosylation reaction has been established by capitalizing on the comproportionation reaction of 2-aryl-1,3-dithiane 1-oxides promoted by triflic anhydride (Tf2O). By wedding the high potency of thiophilic promoter system with the step efficiency of dehydrative glycosylation, this reagent underwent facile intermolecular oxothio acetalization with C1-hemiacetal donor to install a temporary leaving group, rendering a transient electrophilic center at the remote site to the anomeric position. The sulfenyl triflate tethered at the terminus concomitantly activated the sulfide intramolecularly to afford the oxocarbenium ion, thereby facilitating the title glycosylation. Aside from accommodating broad range functional groups and inactive hemiacetal substrates, the present activation protocol also proved expedient for 1,3-diol protection. Most importantly, this method further provided a fresh perspective for the application of sulfur chemistry to carbohydrate chemistry.
- Cai, Lei,Zeng, Jing,Li, Ting,Xiao, Ying,Ma, Xiang,Xiao, Xiong,Zhang, Qin,Meng, Lingkui,Wan, Qian
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supporting information
p. 43 - 49
(2019/11/28)
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- Chemical glucosylation of pyridoxine
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The chemical synthesis of pyridoxine-5′-β-D-glucoside (5′-β-PNG) was investigated using various glucoside donors and promoters. Hereby, the combination of α4,3-O-isopropylidene pyridoxine, glucose vested with different leaving and protecting groups and the application of stoichiometric amounts of different promoters was examined with regards to the preparation of the twofold protected PNG. Best results were obtained with 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl fluoride and boron trifluoride etherate (2.0 eq.) as promoter at 0 °C (59%). The deprotection was accomplished stepwise with potassium/sodium hydroxide in acetonitrile/water followed by acid hydrolysis with formic acid resulting in the chemical synthesis of 5′-β-PNG.
- Bachmann, Thomas,Rychlik, Michael
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supporting information
(2020/02/13)
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- Short gram-scale synthesis of sulfavant A
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Recently, we reported the promising activity of a novel class of sulfoquinovosyl-diacylglycerols named Sulfavants as molecular vaccine adjuvants. Herein, we describe a modified and improved chemical synthesis of the lead product Sulfavant A (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical development. Starting from the versatile synthesis based on the trichloroacetimidate methodology, up-scaled preparation of Sulfavant A (1) was achieved in 11 steps by elimination and modification of those reactions that negatively affected the overall yield by the previous procedure. The novel strategy gave 17% overall yield of the target compound 1 and also paved the way for the gram-scale preparation of a wide range of other charged and neutral glycoglycerolipids.
- Ziaco, Marcello,Fioretto, Laura,Nuzzo, Genoveffa,Fontana, Angelo,Manzo, Emiliano
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p. 2728 - 2733
(2020/11/18)
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- Synthesis and cytotoxic property of annonaceous acetogenin glycoconjugates
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Background: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated. Methods: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay. Results: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS). Conclusion: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.
- Shi, Jing-Fang,Wu, Ping,Cheng, Xiao-Li,Wei, Xiao-Yi,Jiang, Zi-Hua
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p. 4993 - 5004
(2020/11/23)
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- Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation
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Thirty novel 20 (S)–O-linked camptothecin (CPT) glycoconjugates were synthesized. They showed more potent in vitro cytotoxicities over irinotecan, but very weak direct topoisomerase I (Topo I) inhibition was observed at 100.0 μM. Oligosaccharide types, length of a PEG linker and acetyl groups exerted obvious effects on cytotoxicity, selectivity, water solubility and stability of the newly synthesized CPT glycoconjugates. Construct 40, with a bleomycin (BLM) disaccharide linked to diethylene glycol in the introduced ester moiety, demonstrated a superior antitumor activity and a distinct selectivity compared to CPT. No toxicity was detectable in animal acute toxicity intravenously (160 mg/kg). Collectively, attachment of oligosaccharides with tumor targeting to 20 (S)–OH of CPT could offer a solution to the daunting problems posed by current Topo I poisons.
- Li, Maolin,Ye, Wenchong,Fu, Kaishuo,zhou, Cui,Shi, Yonghui,Huang, Weiping,Chen, Wenming,Hu, Jiliang,Jiang, Zhilin,Zhou, Wen
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- Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation
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Several glycoconjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with a 1,2,3-triazolyl moiety were synthesized, and their cytotoxicity was evaluated against some human cancer and normal cell lines. Most of the synthesized compounds demonstrated weak inhibitory activities against the M-HeLa and MCF-7 human cancer cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity against M-HeLa cells (IC50 = 1.7-1.9 μM) that corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell line (IC50 = 3.0 μM). It was found that cytotoxic activity of the lead compounds is due to induction of apoptosis proceeding along the mitochondrial pathway. The present findings suggest that 1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are a promising scaffold for the design of novel anticancer agents.
- Andreeva, Olga V.,Garifullin, Bulat F.,Sharipova, Radmila R.,Strobykina, Irina Yu.,Sapunova, Anastasiya S.,Voloshina, Alexandra D.,Belenok, Mayya G.,Dobrynin, Alexey B.,Khabibulina, Leysan R.,Kataev, Vladimir E.
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p. 2367 - 2380
(2020/08/28)
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- Pivaloyl-protected glucosyl iodide as a glucosyl donor for the preparation of β-C-glucosides
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A method for the selective synthesis of β-C-glucosides using α-D-tetra-O-pivaloylglucosyl iodide as a glucosyl donor is reported. Its diastereoselectivity differs from that of the respective acetyl-protected glucosyl bromide, as it reported in the literature under similar reaction conditions. The concentration of the catalyst, the solvent and the type of additive used are crucial factors that determine the reaction selectivity. This method has been applied in a short synthesis of dapagliflozin. The stability of α-D-tetra-O-pivaloylglucosyl iodide in CDCl3 and THF at reflux was also studied. All side products in the coupling and decomposition reactions were isolated and characterized, and possible pathways for their formation are proposed.
- Triantakonstanti, Virginia V.,Toskas, Alexandros,Iordanidis, Nicolaos S.,Andreou, Thanos,Koftis, Theoharis V.,Gallos, John K.
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supporting information
(2020/07/13)
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- A Dinuclear Dysprosium Complex as an Air-Stable and Recyclable Catalyst: Applications in the Deacetylation of Carbohydrate, Aliphatic, and Aromatic Molecules
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Two dinuclear DyIII complexes, [Dy2(hmb)2(OTf)2(H2O)4]?HOTf?2 THF (A?HOTf?2 THF) and [Dy2(hmi)3(H2O)2]?2 HOTf (B?2 HOTf), have been synthesized by the reaction of Dy(OTf)3 and the Schiff-base ligands H2hmb (N′-(2-hydroxy-3-methoxybenzylidene)benzohydrazide) or H2hmi ((2-hydroxy-3-methoxyphenyl)methylene isonicotinohydrazine). Disarmed glycosyl trichloroacetimidates can be activated by complex A in the synthesis of 1,2-trans-glycosides with primary and secondary acceptors. This method offers an efficient route to selectively deacetylated monosaccharides and disaccharides in high yields and a green catalyst that can be easily recycled and reused.
- Chiu, Ting-Yu,Chin, Wei,Guo, Jiun-Rung,Liang, Chien-Fu,Lin, Po-Heng
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supporting information
p. 627 - 633
(2019/02/09)
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- Chemical synthesis method of Bacillus pyocyaneus 011 serotype O antigen oligosaccharide
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The invention discloses a chemical synthesis method of Bacillus pyocyaneus 011 serotype O antigen oligosaccharide, and belongs to the field of chemistry. The method comprises the steps that a D-glucose block, an L-fucosamine block and a D-fucosimide block are utilized to construct O antigen trisaccharide, wherein the D-glucose block or the L-fucosamine block is connected with the D-fucosimide block through a 1,2-alpha-cis-glycosidic bond, the D-glucose block is connected with the L-fucososamine block through a 1,2-alpha-trans-glycosidic bond, and the 1,2-alpha-cis-glycosidic bond is constructed in a mixed solvent; the mixed solvent comprises two or more of dichloromethane, diethyl ether and thiophene. The method has the advantages that D-mannose is utilized as a raw material to obtain D-fucose simply, conveniently and efficiently; the uniform construction of the cis-glycosidic bond is achieved by relying on the appropriate mixed solvent; the stereoselectivity can reach 100%; and the method has a good application prospect in the development of novel drugs and vaccines for resisting Bacillus pyocyaneus and the like.
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Paragraph 0047; 0051
(2019/05/04)
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- Synthesis and Biological Activity of 3,4,-Tri-О-Acetyl-N-Acetylglucosamine and Tetraacetylglucopyranose Conjugated with Alkyl Phosphates
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Abstract: Conjugates of 3,4,6-tri-О-acetyl-N-acetylglucosamine and tetraacetyl glucopyranose with alkyl phosphates were synthesized. The dependence of their antibacterial and antituberculosis activities on the length of the alkyl substituent at the phosphate group was found. The conjugates with a decyl substituent exhibited in vitro the highest antituberculosis activity against Mycobacterium tuberculosis H37Rv (MIC 3?μg/mL) but the weakest effect towards Streptococcus aureus and Bacillus cereus (≤MIC 125 μg/mL). Vice versa, the conjugates with a cetyl substituent demonstrated the highest antibacterial activity in vitro towards S. aureus and B. cereus (MIC 16 μg/mL) but showed the lowest antituberculosis activity (MIC 12 μg/mL) among the compounds under study.
- Sharipova,Garifullin,Sapunova,Voloshina,Kravchenko,Kataev
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p. 155 - 164
(2019/06/14)
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- GLUCOSAMINE DERIVATIVES AND PHARMACEUTICAL USES THEREOF
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There are provided compounds of Formula (A) and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for the prevention or treatment in a mammal of joint and bone disorders such as arthritis and osteoporosis.
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Paragraph 0209
(2019/07/03)
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- Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy
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Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives (7a-e) were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (8a-e). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties. Among all synthesized glycopeptides, only 8a exhibited increased cytotoxicity (IC50 = 9.6 ± 0.3 μM) and selectivity (IC50 = 37.4 ± 5.9 μM). The glucose transporter 1 (GLUT1) with high expression in cancer cells was approved to be involved in the cytotoxicity and selectivity enhancement of 8a. Furthermore, 8a but not R-lycosin-I inhibited tumor growth in the nude mice xenograft model without generating side effects intraperitoneally. Taken together, this study reveals the different monosaccharide roles in peptide modification and also provides an optimized anticancer peptide with high activity and selectivity, that is, 8a might be a promising lead for developing anticancer drugs.
- Zhang, Peng,Ma, Jing,Zhang, Qianqian,Jian, Shandong,Sun, Xiaoliang,Liu, Bobo,Nie, Liqin,Liu, Meiyan,Liang, Songping,Zeng, Youlin,Liu, Zhonghua
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p. 7857 - 7873
(2019/10/11)
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- COMPOSITIONS AND METHODS OF MODULATING THE IMMUNE RESPONSE BY ACTIVATING ALPHA PROTEIN KINASE 1
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The disclosure provides compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A1, A2, L1, L2, L3, Z1, Z2, W1, W2, R1, R2, R3, R4, R5, R6 and R7 are defined herein.
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Paragraph 229
(2019/05/15)
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- MONOSACCHARIDE PHOSPHORAMIDATE PRODRUGS
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The present disclosure provides monosaccharide phosphoramidate prodrugs of monosaccharide monophosphates. The present disclosure further provides methods of treating diseases of conditions such as congenital disorders of glycosylation comprising administering the monosaccharide phosphoramidate prodrugs of the present disclosure to a patient in need thereof.
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Paragraph 0149; 0176
(2019/07/19)
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- Conformational analysis of the disaccharide methyl a-d-mannopyranosyl-(1→3)-2-O-acetyl-β-D-manno-pyranoside monohydrate
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The crystal structure of methyl β-d-mannopyranosyl-(1→3)-2-O-acetyl-β-d-mannopyranoside monohydrate, C15H26O12.H2O, (II), has been determined and the structural parameters for its constituent β-d-mannopyranosyl residue compared with those for methyl β-d-mannopyranoside. Mono-O-acetylation appears to promote the crystallization of (II), inferred from the difficulty in crystallizing methyl β-d-mannopyranosyl-(1→3)-β-d-mannopyranoside despite repeated attempts. The conformational properties of the O-acetyl side chain in (II) are similar to those observed in recent studies of peracetylated mannose-containing oligosaccharides, having a preferred geometry in which the C2—H2 bond eclipses the C O bond of the acetyl group. The C2—O2 bond in (II) elongates by ≈0.02 ? upon O-acetylation. The phi (φ) and psi () torsion angles that dictate the conformation of the internal O-glycosidic linkage in (II) are similar to those determined recently in aqueous solution by NMR spectroscopy for unacetylated (II) using the statistical program MA'AT, with a greater disparity found for (? = ≈16°) than for φ (? = ≈6°).
- Zhang, Wenhui,Wu, Qingquan,Oliver, Allen G.,Serianni, Anthony S.
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p. 610 - 615
(2019/06/14)
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- Glucoside derivatives of podophyllotoxin: Synthesis, physicochemical properties, and cytotoxicity
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Background: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied. Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure–activity relationship and the physicochemical property–anticancer activity relationship of these compounds. Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA 2, MW > 700 Da, and RB > 10. Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.
- Zi, Cheng-Ting,Yang, Liu,Kong, Qing-Hua,Li, Hong-Mei,Yang, Xing-Zhi,Ding, Zhong-Tao,Jiang, Zi-Hua,Hu, Jiang-Miao,Zhou, Jun
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p. 3683 - 3692
(2019/11/05)
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- Facile synthesis of sugar lactols via bromine-mediated oxidation of thioglycosides
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Synthesis of a variety of sugar lactols (hemiacetals) has been accomplished in moderate to excellent yields by using bromine-mediated oxidation of thioglycosides. It was found that acetonitrile is the optimal solvent for this oxidation reaction. This approach involving bromine as oxidant is superior to that using N-bromosuccinimide (NBS) which produces byproduct succinimide often difficult to separate from the lactol products.
- Meng, Shuai,Bhetuwal, Bishwa Raj,Acharya, Padam P.,Zhu, Jianglong
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p. 109 - 126
(2019/03/26)
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- Copper-Catalyzed Anomeric O-Arylation of Carbohydrate Derivatives at Room Temperature
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Direct and practical anomeric O-arylation of sugar lactols with substituted arylboronic acids has been established. Using copper catalysis at room temperature under an air atmosphere, the protocol proved to be general, and a variety of aryl O-glycosides have been prepared in good to excellent yields. Furthermore, this approach was extended successfully to unprotected carbohydrates, including α-mannose, and it was demonstrated here how the interaction between carbohydrates and boronic acids can be combined with copper catalysis to achieve selective anomeric O-arylation.
- Verdelet, Tristan,Benmahdjoub, Sara,Benmerad, Belkacem,Alami, Mouad,Messaoudi, Samir
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p. 9226 - 9238
(2019/08/12)
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- Towards a Synthetic Strategy for the Ten Canonical Carrageenan Oligosaccharides – Synthesis of a Protected γ-Carrageenan Tetrasaccharide
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Herein, we report a synthetic strategy aiming at synthesizing the ten canonical carrageenan oligosaccharides from one single precursor. The key β-(1→4)-linked disaccharide was synthesized from commercially available galactose pentaacetate. The notoriously difficult formation of β-(1→4)-d-galactan linkages was successfully optimized on the differentially substituted monosaccharides to afford the desired disaccharide in 55 % yield. Following a convergent strategy, two disaccharides were then glycosylated to form the fully protected α-(1→4)-linked tetrasaccharide backbone of the carrageenans. The careful selection of protecting groups provides the opportunity to access all ten carrageenan substructures identified in polysaccharides isolated from red algae. Here, we demonstrate how one such target oligosaccharide can be obtained in a protected form.
- Kinnaert, Christine,Clausen, Mads H.
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supporting information
p. 3236 - 3243
(2019/06/08)
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- Design, synthesis and bioactivity of core 1 O-glycan and its derivative on human gut microbiota
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Background: Disaccharide core 1 (Galβ1-3GalNAc) is a common O-glycan structure in nature. Biochemical studies have confirmed that the formation of the core 1 structure is an important initial step in O-glycan biosynthesis and it is of great importance for human body. Objective: Our study will provide meaningful and useful sights for O-glycan synthesis and their bioassay. And all the synthetic glycosides would be used as intermediate building blocks in the scheme developed for oligosaccharide construction. Methods: In this article, we firstly used chemical procedures to prepare core 1 and its derivative, and a novel disaccharide was efficiently synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR and MS. Then we employed three human gut symbionts belonging to Bacteroidetes, a predominantphyla in the distal gut, as models to study the bioactivity of core 1 and its derivative on human gut microbiota. Results: According to our results, both core 1 and derivative could support the growth of B. fragilis, especially the core 1 derivative, while failed to support the growth of B. thetaiotaomicron and B. ovatus. Conclusion: This suggested that the B. fragilis might have the specificity glycohydrolase to cut the glycosidic bond for acquiring monosaccharide.
- Qu, Huanhuan,Li, Baixue,Yang, Jingyi,Liang, Huaiwen,Li, Meixia,Ding, Kan
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p. 1348 - 1353
(2019/11/22)
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- Synthesis and O-Glycosidic Linkage Conformational Analysis of 13C-Labeled Oligosaccharide Fragments of an Antifreeze Glycolipid
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NMR studies of two 13C-labeled disaccharides and a tetrasaccharide were undertaken that comprise the backbone of a novel thermal hysteresis glycolipid containing a linear glycan sequence of alternating [βXylp-(1→4)-βManp-(1→4)]n dimers. Experimental trans-glycoside NMR J-couplings, parameterized equations obtained from density functional theory (DFT) calculations, and an in-house circular statistics package (MA'AT) were used to derive conformational models of linkage torsion angles φ and ψ in solution, which were compared to those obtained from molecular dynamics simulations. Modeling using different probability distribution functions showed that MA'AT models of φ in βMan(1→4)βXyl and βXyl(1→4)βMan linkages are very similar in the disaccharide building blocks, whereas MA'AT models of ψ differ. This pattern is conserved in the tetrasaccharide, showing that linkage context does not influence linkage geometry in this linear system. Good agreement was observed between the MA'AT and MD models of ψ with respect to mean values and circular standard deviations. Significant differences were observed for φ, indicating that revision of the force-field employed by GLYCAM is probably needed. Incorporation of the experimental models of φ and ψ into the backbone of an octasaccharide fragment leads to a helical amphipathic topography that may affect the thermal hysteresis properties of the glycolipid.
- Zhang, Wenhui,Meredith, Reagan,Yoon, Mi-Kyung,Wang, Xiaocong,Woods, Robert J.,Carmichael, Ian,Serianni, Anthony S.
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p. 1706 - 1724
(2019/02/14)
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- Camptothecin sugar derivative and preparation method and application thereof
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The invention relates to a camptothecin sugar derivative and a preparation method and application thereof, and belongs to the field of biological medicines. The structural formula of the camptothecinsugar derivative is shown in formula (I) in specification. The camptothecin sugar derivative can obviously improve the stability and water solubility of camptothecin and 10-hydroxycamptothecin, and has different sensitivities to different tumor cells. Especially when the chain link n equals to 1, the camptothecin sugar derivative of the invention can significantly increase the selectivity to tumorcells.
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Paragraph 0062-0064
(2019/11/13)
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