A5089718159- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- X-ray Diffraction in Crystallography
- Enzyme Production and Characterization
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Lysosomal Storage Disorders Research
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- Organic and Inorganic Chemical Reactions
- Legume Nitrogen Fixing Symbiosis
- Sulfur-Based Synthesis Techniques
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Enzyme Catalysis and Immobilization
- Synthesis and Characterization of Heterocyclic Compounds
- Click Chemistry and Applications
- RNA Interference and Gene Delivery
- Chemical Synthesis and Reactions
- Studies on Chitinases and Chitosanases
- Synthesis and Catalytic Reactions
- Organic Chemistry Cycloaddition Reactions
- Catalytic C–H Functionalization Methods
- Oxidative Organic Chemistry Reactions
Institut de Chimie des Milieux et des Matériaux de Poitiers
2015-2025
Université de Poitiers
2015-2025
Centre National de la Recherche Scientifique
2014-2024
Laboratoire de Synthèse Organique
2014-2019
Département de Chimie Moléculaire
2005-2016
Université Grenoble Alpes
2008-2016
International Council on Mining and Metals
2015
Institut Lavoisier de Versailles
2012
Département de Pharmacochimie Moléculaire
2005-2012
Université de Picardie Jules Verne
2010
The broad application of well-defined synthetic oligosaccharides in glycobiology and glycobiotechnology is largely hampered by the lack sufficient amounts carbohydrate specimens. Insufficient knowledge glycosylation reaction mechanism thwarts routine assembly these materials. Glycosyl cations are key reactive intermediates reaction, but their high reactivity fleeting nature have precluded determination clear structure-reactivity-stereoselectivity principles for species. We report a combined...
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 consequence deoxygenation halogen substitution at C2 position a series 2-halogenoglucosyl, galactosyl, mannosyl donors condensed phase. These cationic intermediates were characterized using low-temperature situ NMR experiments supported by DFT calculations. The 2-bromo derivatives display...
Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site 16S rRNA. Decades widespread clinical use AGs strongly reduced their efficacy selection resistant bacteria. Recently, conjugation lipophilic groups generated novel class antibacterial amphiphilic aminoglycosides (AAGs) with significant improved activities against various sensitive bacterial strains. We have identified 3',6-dialkyl derivatives...
Abstract The transformation of glycals into 2,3‐unsaturated glycosyl derivatives, reported by Ferrier in 1962, is supposed to involve an α,β unsaturated cation, elusive ionic species that has still be observed experimentally. Herein, while combination TfOH and flow conditions failed observe this species, its extended lifetime superacid solutions allowed characterization NMR‐based structural analysis supported DFT calculations. This allyloxycarbenium ion was further exploited the...
The neamine part of the aminoglycoside antibiotic neomycin B was conjugated to a 16 mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. Attachment core allows cellular uptake PNA and results in potent inhibition replication. polycationic moiety imparts greater solubility also confers unique RNA cleavage property conjugate which is specific its target site functional at physiological concentrations Mg2+. These properties suggest potential therapeutic application for this class compounds.
A flexible synthetic access to six-membered l- and d-iminosugar C-glycosides is reported starting from the easily available 6-azido-6-deoxy-2,3,4-tri-O-benzyl-d-glucopyranose precursor. This methodology involves a highly diastereoselective tandem ring enlargement/alkylation stereocontrolled contraction. It allows an efficient synthesis of iminosugar displaying structural diversity at both C-1 C-6.
The one-pot two-step stereoselective synthesis of 1,2-trans-1-C-1,3-dithian-2-yl and 1,2-cis-1-C-nitromethyl iminosugars from sugar lactams is disclosed, exploiting Schwartz's reagent triggered amide to imine reduction followed by Corey-Seebach or nitro-Mannich-mediated functionalizations. Processing the dithiane moiety provided naturally occurring β-HNJ α-HMJ homoiminosugars, while processing nitromethyl group gave access α-HNJ pipecolic acid derivatives. Epimerization this function was...
The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. For this purpose, we prepared aminoglucosamine monomer 15 and attached it protected PNA prior its cleavage from solid support. We found that resulting PNA-aminoglucosamine conjugate is stable under acidic conditions, efficiently taken up by human cells fairly distributed in both cytosol nucleus without endosomal entrapment because...
Abstract A set of multivalent polyhydroxylated acetamidoazepanes based on ethylene glycol, glucoside, or cyclodextrin scaffolds was prepared. The compounds were assessed against plant, mammalian, and therapeutically relevant hexosaminidases. Multimerization shown to improve the inhibitory potency with synergy, fine tune selectivity profile between related
The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. key step to prepare these α-d-GlcNAc and α-d-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied azepane precursor. This strategy also allows access naturally occurring α-HGJ α-HNJ. α-d-GlcNAc-configured iminosugar was coupled glucoside acceptor yield novel pseudodisaccharide. Preliminary glycosidase inhibition evaluation indicates that α-d-GalNAc-configured homoiminosugar...
The glycosidase inhibitory properties of synthetic C-alkyl and N-alkyl six-membered iminosugars have been extensively studied leading to therapeutic candidates. related seven-membered iminocyclitols less examined despite the report promising structures. Using an in house ring enlargement/C-alkylation as well cross-metathesis methodologies key steps, we undertaken synthesis biological evaluation a library fourteen 2C- eight tetrahydroxylated azepanes starting from easily available...
A series of 3-substituted (aryloxy)silane derivatives benzylamine (4, 4', or 4") was synthesized and evaluated for hypocholesterolemic activity. Most the new silane were identified as potent inhibitors pig liver squalene epoxidase with IC50 values in submicromolar range. In vitro inhibition cholesterol biosynthesis Hep-G2 cells observed a very good potency ene-yne 4a, 4i, 4n, 4q, 4u well yne-yne compound 4". vivo, 4u, 4" found to decrease rats upon oral administration ED50 range 2-7 mg/kg....
In earlier studies, we found that a conjugate of neamine-polyamide nucleic acid targeting transactivation response element HIV-1 RNA genome (HIV-1 TAR) displayed anti-HIV-1 activity and sequence-specific cleavage the target in vitro. Here show both position conjugation polyamide (PNA) on neamine length spacer are critical parameters for conferring to conjugate. The PNA via incorporating 11 atoms 5-position ring I core conferred conjugate, while 4′-position II abolished this activity....
The first synthesis of 1,2-trans-homoiminosugars devised as mimics β-d-GlcNAc and α-d-ManNAc is described. Key steps include a regioselective azidolysis cyclic sulfite β-amino alcohol skeletal rearrangement applied to polyhydroxylated azepane. derivative has been coupled serine deliver an iminosugar C-amino acid. two homoiminosugars demonstrate moderate glycosidase inhibition.
Synthetic DNJs bearing a thiolated, fluorinated or unsaturated<italic>N</italic>-substituent exhibit trehalase inhibition F508del-CFTR correction.
NagZ is an N-acetyl-β-d-glucosaminidase that participates in the peptidoglycan (PG) recycling pathway of Gram-negative bacteria by removing N-acetyl-glucosamine (GlcNAc) from PG fragments have been excised cell wall during growth. The 1,6-anhydromuramoyl-peptide products generated activate β-lactam resistance many inducing expression AmpC β-lactamase. Blocking activity can thereby suppress antibiotic these bacteria. active site dynamic and it accommodates distortion glycan substrate...
DMDP amide restored Hex A activity in the G269S Tay–Sachs patient cells up to 43% of wild type.
A new family of chiral C2 symmetric tetraazamacrocycles, coined ISAC for IminoSugar Aza-Crown, incorporating two iminosugars adopting a 4C1 conformation is disclosed. Multinuclear NMR experiments on the corresponding Cd2+ complex show that strong chelator in water and its tetramine cavity adopts similar to parent Cd–cyclam complex. Similar behavior observed with Cu2+ solution, enhanced stability compared Cu–cyclam
Abstract The synthesis of new β‐cyclodextrin dimers linked through their primary faces by different glycerol‐like moieties click chemistry is described. unusual behaviour these cyclodextrin–glycerol in aqueous solution has been studied NMR spectroscopy. We show that, depending on the length linking arm between two cyclodextrins, could adopt very conformations water: symmetrical or pseudo[1]rotaxane‐like structures one D ‐glucopyranose unit tumbling β‐cyclodextrin.