141395-48-4Relevant articles and documents
Polyfluoroglycoside Synthesis via Simple Alkylation of an Anomeric Hydroxyl Group: Access to Fluoroetoposide Analogues
Tremblay, Thomas,St-Gelais, Jacob,Houde, Maxime,Giguere, Denis
, p. 4812 - 4824 (2021/04/02)
In this work, we have developed a new approach for the synthesis of fluoroglycoside analogues. This strategy used a simple alkylation protocol and allowed the installation of a simple aglyconic alkane with the β configuration. Moreover, the glycosylation of fluorinated glucoside analogues with 4′-demethylepipodophyllotoxin furnished novel fluoroetoposide analogues. In these cases, the α anomers were formed as major products with an S configuration at the C-4 of the aglycone.
Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects
St-Gelais, Jacob,C?té, émilie,Lainé, Danny,Johnson, Paul A.,Giguère, Denis
, p. 13499 - 13506 (2020/10/02)
In this work, we synthesized all mono-, di-, and trifluorinated glucopyranose analogues at positions C-2, C-3, C-4, and C-6. This systematic investigation allowed us to perform direct comparison of 19F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C-6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web-based programs.
Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions
Denavit, Vincent,Lainé, Danny,Bouzriba, Chahrazed,Shanina, Elena,Gillon, émilie,Fortin, Sébastien,Rademacher, Christoph,Imberty, Anne,Giguère, Denis
supporting information, p. 4478 - 4490 (2019/03/07)
The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono- and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach. Given the scarcity of these compounds in the literature, in addition to their synthesis, their biological profiles were evaluated. Firstly, the fluorinated compounds were investigated as antiproliferative agents using normal human and mouse cells in comparison with cancerous cells. Most of the fluorinated compounds showed no antiproliferative activity. Secondly, these carbohydrate probes were used as potential inhibitors of galactophilic lectins. The first transverse relaxation-optimized spectroscopy (TROSY) NMR experiments were performed on these interactions, examining chemical shift perturbations of the backbone resonances of LecA, a virulence factor from Pseudomonas aeruginosa. Moreover, taking advantage of the fluorine atom, the 19F NMR resonances of the monofluorogalactopyranosides were directly monitored in the presence and absence of LecA to assess ligand binding. Lastly, these results were corroborated with the binding potencies of the monofluorinated galactopyranoside derivatives by isothermal titration calorimetry experiments. Analogues with fluorine atoms at C-3 and C-4 showed weaker affinities with LecA as compared to those with the fluorine atom at C-2 or C-6. This research has focused on the chemical synthesis of “drug-like” low-molecular-weight inhibitors that circumvent drawbacks typically associated with natural oligosaccharides.
Structural and Computational Analysis of 2-Halogeno-Glycosyl Cations in the Presence of a Superacid: An Expansive Platform
Lebedel, Ludivine,Ardá, Ana,Martin, Amélie,Désiré, Jér?me,Mingot, Agnès,Aufiero, Marialuisa,Aiguabella Font, Nuria,Gilmour, Ryan,Jiménez-Barbero, Jesus,Blériot, Yves,Thibaudeau, Sébastien
supporting information, p. 13758 - 13762 (2019/08/21)
An expansive NMR-based structural analysis of elusive glycosyl cations derived from natural and non-natural monosaccharides in superacids is disclosed. For the first time, it has been possible to explore the consequence of deoxygenation and halogen substitution at the C2 position in a series of 2-halogenoglucosyl, galactosyl, and mannosyl donors in the condensed phase. These cationic intermediates were characterized using low-temperature in situ NMR experiments supported by DFT calculations. The 2-bromo derivatives display intramolecular stabilization of the glycosyl cations. Introducing a strongly electron-withdrawing fluorine atom at C2 exerts considerable influence on the oxocarbenium ion reactivity. In a superacid, these oxocarbenium ions are quenched by weakly coordinating SbF6? anions, thereby demonstrating their highly electrophilic character and their propensity to interact with poor nucleophiles.
KinITC—One Method Supports both Thermodynamic and Kinetic SARs as Exemplified on FimH Antagonists
Zihlmann, Pascal,Silbermann, Marleen,Sharpe, Timothy,Jiang, Xiaohua,Mühlethaler, Tobias,Jakob, Roman P.,Rabbani, Said,Sager, Christoph P.,Frei, Priska,Pang, Lijuan,Maier, Timm,Ernst, Beat
, p. 13049 - 13057 (2018/08/17)
Affinity data, such as dissociation constants (KD) or inhibitory concentrations (IC50), are widely used in drug discovery. However, these parameters describe an equilibrium state, which is often not established in vivo due to pharmacokinetic effects and they are therefore not necessarily sufficient for evaluating drug efficacy. More accurate indicators for pharmacological activity are the kinetics of binding processes, as they shed light on the rate of formation of protein–ligand complexes and their half-life. Nonetheless, although highly desirable for medicinal chemistry programs, studies on structure–kinetic relationships (SKR) are still rare. With the recently introduced analytical tool kinITC this situation may change, since not only thermodynamic but also kinetic information of the binding process can be deduced from isothermal titration calorimetry (ITC) experiments. Using kinITC, ITC data of 29 mannosides binding to the bacterial adhesin FimH were re-analyzed to make their binding kinetics accessible. To validate these kinetic data, surface plasmon resonance (SPR) experiments were conducted. The kinetic analysis by kinITC revealed that the nanomolar affinities of the FimH antagonists arise from both (i) an optimized interaction between protein and ligand in the bound state (reduced off-rate constant koff) and (ii) a stabilization of the transition state or a destabilization of the unbound state (increased on-rate constant kon). Based on congeneric ligand modifications and structural input from co-crystal structures, a strong relationship between the formed hydrogen-bond network and koff could be concluded, whereas electrostatic interactions and conformational restrictions upon binding were found to have mainly an impact on kon.
Synthesis of substrate analogues as potential inhibitors for Mycobacterium tuberculosis enzyme MshC
Patel, Krishnakant,Song, Fengling,Andreana, Peter R.
, p. 10 - 18 (2017/11/07)
Mycothiol cysteine ligase (MshC) is a key enzyme in the mycothiol (MSH) biosynthesis and a promising target for developing new anti-mycobacterial compounds. Herein, we report on the synthesis of substrate analogues, as potential inhibitors, for the MshC e
Phosphodiesters serve as potentially tunable aglycones for fluoro sugar inactivators of retaining β-glycosidases
Rempel,Withers
, p. 2592 - 2595 (2014/04/17)
2-Deoxy-2-fluoroglycosides bearing dibenzyl phosphate and phosphonate aglycones were synthesised and tested as covalent inactivators of several retaining α- and β-glycosidases. β-d-Gluco-, -manno- and -galacto-configured benzyl-benzylphosphonate derivatives efficiently inactivated β-gluco-, β-manno- and β-galactosidases, while α-gluco- and α-manno-configured phosphate and phosphonate derivatives served instead as slow substrates. This journal is the Partner Organisations 2014.
Fluorine-directed β-galactosylation: Chemical glycosylation development by molecular editing
Durantie, Estelle,Bucher, Christoph,Gilmour, Ryan
supporting information; experimental part, p. 8208 - 8215 (2012/08/27)
Validation of the 2-fluoro substituent as an inert steering group to control chemical glycosylation is presented. A molecular editing study has revealed that the exceptional levels of diastereocontrol in glycosylation processes by using 2-fluoro-3,4,6-tri-O-benzyl glucopyranosyl trichloroacetimidate (TCA) scaffolds are a consequence of the 2R,3S,4S stereotriad. This study has also revealed that epimerization at C4, results in a substantial enhancement in β-selectivity (up to β/α 300:1). Copyright
Selenenylsulfide-linked homogeneous glycopeptides and glycoproteins: Synthesis of human "hepatic Se MetaboliteA"
Boutureira, Omar,Bernardes, Gonacalo J. L.,Fernandez-Gonzalez, Marta,Anthony, Daniel C.,Davis, Benjamin G.
scheme or table, p. 1432 - 1436 (2012/03/27)
Introducing selenium: The synthesis and full characterization of human hepatic Se metaboliteA has been accomplished by using a robust, efficient, and Cys-specific selenenylation protocol (see scheme; NaPi=sodium phosphate). The selenenylsulfide linkage is sufficiently stable to allow quantification of Se-containing glycoconjugates in biological fluids by using atomic detection methods. Copyright
Synthesis of nonnatural nucleoside diphosphate sugars
Wolf, Saskia,Berrio, Rosmirt Molina,Meier, Chris
, p. 6304 - 6313 (2011/12/16)
Recently, we reported an efficient chemical method for the synthesis of a variety of naturally occurring nucleoside diphosphate (NDP) sugars. This method, which is based on the cycloSal approach, can also be used, in principle, for the preparation of rare or even nonnatural NDP sugars. Herein, the syntheses of sulfoquinovose-, glucose-6-sulfate-, L-galactose-, and 2-fluoroglycopyranoside- containing NDP sugars are presented, as well as the synthesis of NDP sugars with non-natural nucleosides. The reactions described gavestereoisomerically defined NDP sugars in high yields and short reaction times.
