A5103072907- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Cyclopropane Reaction Mechanisms
- Synthetic Organic Chemistry Methods
- RNA and protein synthesis mechanisms
- Advanced MRI Techniques and Applications
- Catalytic Alkyne Reactions
- Chemical synthesis and alkaloids
- Advanced Synthetic Organic Chemistry
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Advanced Neuroimaging Techniques and Applications
- Crystallography and molecular interactions
- Glioma Diagnosis and Treatment
- Multicomponent Synthesis of Heterocycles
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Neonatal and fetal brain pathology
- Synthesis of Organic Compounds
- Fetal and Pediatric Neurological Disorders
- RNA Research and Splicing
- Hedgehog Signaling Pathway Studies
- Catalytic C–H Functionalization Methods
Université de Strasbourg
2016-2025
Centre National de la Recherche Scientifique
2013-2024
Laboratoire d'Innovation Thérapeutique
2014-2024
Université de Montréal
2011-2021
Pharmac
2014-2020
Hôpital de la Timone
2007-2017
Aix-Marseille Université
2017
Centre de Résonance Magnétique Biologique et Médicale
2007-2017
Centre National pour la Recherche Scientifique et Technique (CNRST)
2015
Université de Rennes
2005-2014
The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) have emerged as key mediators in the pathophysiology of several mood disorders, including anxiety depression. However, therapeutic compounds that interact with TrkB receptors been difficult to develop. Using a combination structure-based silico screening high-capacity functional assays recombinant neuronal cells, we identified low-molecular weight ligand (ANA-12) prevented...
Abstract Purpose To assess the combined value of diffusion‐weighted imaging (DWI) and proton magnetic resonance spectroscopy ( 1 H‐MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, infiltrating glioma a pediatric population. Materials Methods A total 17 children with untreated posterior fossa tumors (seven four glioma, two astrocytoma), were investigated conventional MRI, DWI, MRS using single‐voxel technique. Within nonnecrotic tumor core, apparent diffusion...
The Smoothened (Smo) receptor, a member of class F G protein-coupled receptors, is the main transducer Hedgehog (Hh) signaling pathway implicated in wide range developmental and adult processes. Smo target anticancer drugs that bind to long narrow cavity 7-transmembrane (7TM) domain. X-ray structures human (hSmo) bound several ligands have revealed 2 types 7TM-directed antagonists: those binding mostly extracellular loops (site 1, e.g., LY2940680) penetrating deeply 7TM 2, SANT-1). Here we...
Short and efficient access to (+)-lupinine (+)-epiquinamide by means of an unprecedented double hydroformylation a bis-homoallylic azide followed tandem catalytic hydrogenation/reductive bis-amination is reported.
Linear hydroformylation of N-protected allyl- or homoallylamines (cyclohydrocarbonylation: CHC), followed by a reductive amination constitute the two key steps toward convenient routes to aza-heterocycles.
Convenient accesses to enantiomerically pure 2-, 2,3-, 2,6-, 2,3,6-substituted piperidines and 1,4-substituted indolizine are described. At first, indium-mediated aminoallylation -crotylation of aldehydes with (R)-phenylglycinol or (1R,2S)-1-amino-2-indanol gave homoallylamines high stereocontrol. Then, these products, submitted a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation, afforded perhydrooxazolo[3,2-a]piridines whose oxazolidines opened nucleophiles. Finally, the removal...
The development of hydroformylative domino reactions easily accessible vinyl acetamides is described. Extremely regioselective hydroformylation terminal double bounds provides a transient N-acyliminium that can be trapped by various nucleophiles to give several aza-heterocylic scaffolds in diastereoselective manner.
The total syntheses of both enantiomers trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation enantiopure 4-piperidone (-)-11, which prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation-reduction decyanation process. α-Amino at anode electrochemical oxidation (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1-3 stereoinduction,...
Activation of the Smoothened (Smo) receptor mediates Hedgehog (Hh) signaling. Hh inhibitors are in clinical trials for cancer, and small-molecule Smo agonists may have therapeutic interests regenerative medicine. Here, we generated validated a pharmacophoric model used this virtual screening library commercially available compounds. Among 20 top-scoring ligands, identified characterized novel quinolinecarboxamide derivative, propyl...
The Doyle-Kirmse reaction represents a powerful synthetic tool for forming both C-S and C-C bonds in single process. rhodium-catalyzed of S-allyl S-propargyl phosphorothioates with diazoesters has been developed rare example involving substrates bearing an electron withdrawing group on the sulfur atom. transformation takes place at room temperature, only 5 min, leads via [2,3]-sigmatropic rearrangement sulfonium ylide intermediate to corresponding S-homoallyl or S-homoallenyl yields ranging...
We report an Orthogonal Tandem Catalysis (OTC) involving Au(I)-hydroacyloxylation and Rh(I)-hydroformylation highlighting their compatibility when these metals are employed in a reaction of homogeneous catalysis. Moreover, this OTC allows the...
A multicomponent reaction between H2, CO, an unsaturated carboxylic acid derivative, and binucleophiles has been discovered. This process represents a combination of diversity-oriented synthesis reactions including amidation hydroformylation, followed by nucleophilic addition to N-acyliminium ion allowing the generation six new bonds. Using π-nucleophiles, sequence turns into Pictet−Spengler reaction.
Abstract Hedgehog (Hh) is a critical regulator of adipogenesis. Extracellular vesicles are natural Hh carriers, as illustrated by activated/apoptotic lymphocytes specifically shedding microparticles (MP) bearing the morphogen (MP Hh+ ). We show that MP inhibit adipocyte differentiation and orientate mesenchymal stem cells towards pro-osteogenic program. Despite Smoothened (Smo)-dependency, anti-adipogenic effects do not activate canonical signalling pathway in contrast to those elicited...
A multicomponent reaction (MCR) based on a cyclohydrocarbonylation (CHC) driven by hydroformylation was set up toward the efficient diastereoselective preparation of oxazolopiperidines (4a-e) and -azepines (7a-d). The bicyclic oxazolidines were obtained from chiral N-alkenylamino alcohols via transient cyclic iminium intermediates that underwent an intramolecular cyclization appendant oxygen. On basis series different experimental conditions, diastereocontrol observed during formation is...
The rhodium-catalyzed hydroformylation of ynamides is described and gives selective access to 2- or 3-aminoacrolein derivatives. regioselectivity this carbonylation can be completely controlled at will thanks the nature ligand used. This represents first example regiodivergent alkyne hydroformylation. influence substituents on different positions ynamide has been investigated, it appears that reaction tolerant a wide range functional groups.
The Neurospora VS ribozyme is a small nucleolytic with unique primary, secondary and global tertiary structures, which displays mechanistic similarities to the hairpin ribozyme. Here, we determined high-resolution NMR structure of stem-loop VI fragment containing A730 internal loop, forms part active site. In presence magnesium ions, loop adopts that consistent existing biochemical data most likely reflects its conformation in prior docking cleavage site loop. Interestingly, an S-turn motif...
As part of an effort to structurally characterize the complete Neurospora VS ribozyme, NMR solution structures several subdomains have been previously determined, including internal loops domains I and VI, I/V kissing-loop interaction III-IV-V junction. Here, we expand this work by determining structure a 62-nucleotide RNA (J236) that encompasses ribozyme II-III-VI three-way junction its adjoining stems. In addition, localize Mg(2+)-binding sites within using Mn(2+)-induced paramagnetic...