A5060530792- Peptidase Inhibition and Analysis
- Microbial infections and disease research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Antibiotic Resistance in Bacteria
- Chemical Synthesis and Analysis
- HIV/AIDS drug development and treatment
- Microbial Natural Products and Biosynthesis
- Catalytic C–H Functionalization Methods
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Plant biochemistry and biosynthesis
- Alkaloids: synthesis and pharmacology
- Axial and Atropisomeric Chirality Synthesis
- Sulfur-Based Synthesis Techniques
- Synthesis and Catalytic Reactions
- Glycosylation and Glycoproteins Research
- Drug Transport and Resistance Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Pharmacological Effects of Natural Compounds
- Chemical synthesis and alkaloids
- Trypanosoma species research and implications
- Advanced Synthetic Organic Chemistry
- Nanoparticle-Based Drug Delivery
- Oxidative Organic Chemistry Reactions
Centre National de la Recherche Scientifique
2015-2021
Université Paris Sciences et Lettres
2020-2021
ESPCI Paris
2018-2021
ETH Zurich
2015-2018
Génomique Bioinformatique et Applications
2018
Laboratoire de Chimie Moléculaire
2015
Université de Strasbourg
2015
Abstract Axially chiral biaryls are ubiquitous structural motifs of biologically active molecules and privileged ligands for asymmetric catalysis. Their properties due to their configurationally stable axis, therefore, the control absolute configuration is essential. Efficient access atropo‐enantioenriched biaryl moieties through direct C−H activation, by using enantiopure sulfoxide as both directing group (DG) auxiliary, reported. The stereoselective oxidative Heck reactions performed in...
Several of the enzymes related to folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless serine hydroxymethyltransferase (SHMT), one key this cycle, efficient inhibitors have not been described so far. On basis plant SHMT from an herbicide optimization program, highly potent Plasmodium falciparum (Pf) and vivax (Pv) with a pyrazolopyran core structure were identified. Cocrystal structures PvSHMT solved at 2.6 Å resolution. These ligands showed...
Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed improve microsomal metabolic stability and identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) Arabidopsis thaliana (At) SHMT target assays PfNF54 strains cell-based with values low...
Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, metabolic instability. Smart nanocarrier-based drug delivery systems provide means solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol–disulfide exchange reaction between thiolated hydrophilic block pyridyl...
Abstract With the discovery that serine hydroxymethyltransferase (SHMT) is a druggable target for antimalarials, aim of this study was to design novel inhibitors key enzyme in folate biosynthesis cycle. Herein, 19 spirocyclic ligands based on either 2‐indolinone or dihydroindene scaffolds and featuring pyrazolopyran core are reported. Strong affinities Plasmodium falciparum ( Pf ) SHMT (14–76 n m cellular potencies low nanomolar range (165–334 were measured together with interesting...
Abstract Malaria remains a major threat to mankind due the perpetual emergence of resistance against marketed drugs. Twenty‐one pyrazolopyran‐based inhibitors bearing terminal biphenyl, aryl sulfonamide, or sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), key enzyme folate cycle. The best ligands inhibited Plasmodium falciparum ( Pf ) Arabidopsis thaliana At SHMT in target, as well NF54 strains cell‐based assays low nanomolar range (18–56 n m )....
Artemisinin is an important drug to fight malaria. It produced either by extraction or via a semisynthetic route involving enzyme engineering. A key intermediate produce artemisinin the enzymatic dihydroartemisinic aldehyde (DHAAl). However, control of absolute configuration stereocenter α highly challenging. Herein we report protocol that allows diastereomeric enrichment mixture (11R)/(11S)-DHAAl desired (11R)-DHAAl utilizing crystallization-induced diastereomer transformation induced Betti...
A new access to artemisinin is reported based on a selective photochemical hydrothiolation of amorphadiene, waste product the industrial semisynthetic route. This study highlights discovery two distinctive activation pathways under solvent-free conditions or using photocatalyst promoting H-abstraction. Subsequently, chemoselective oxidation resulting photochemically generated thioether, followed by Pummerer rearrangement, affords dihydroartemisinic aldehyde, key intermediate in synthesis artemisinin.
GRAPHICAL ABSTRACT
A formal synthesis of artemisinin starting from amorphadiene is described. This new route relies on the development a catalytic chemo- and diastereoselective hydrosilylation. The practicability this method demonstrated by converting to dihydroartemisinic aldehyde using one-pot hydrosilylation/oxidation sequence, minimizing number purifications maximizing productivity through practical procedure. In addition, approach can be coupled with crystallization-induced transformation (CIDT) enhance...
Amorphadiene is a natural product involved in the biosynthesis of antimalarial drug artemisinin. A convenient four-step synthesis amorphadiene, starting from commercially available dihydroartemisinic acid, reported. The targeted molecule isolated with an overall yield 85% on multi-gram scale four steps only one chromatography.
A regioselective Pd-catalyzed allylic oxidation of amorphadiene, a key precursor to the antimalarial drug artemisinin, is described. Amorphadiene can be obtained in high yields by fermentation, but it currently treated as waste industrial semisynthetic artemisinin process. The catalytic step described here substitute for P450 enzymes involved biosynthesis and opens up new opportunities supplement critical current route increase potential fermentation
Abstract Access to atropo‐enantioenriched chiral biaryl moieties through asymmetric direct C—H activation is achieved using an enantiopure sulfoxide as both the directing group and auxiliary.