A5008400616- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Sulfur-Based Synthesis Techniques
- Genomics and Phylogenetic Studies
- Catalytic C–H Functionalization Methods
- Radical Photochemical Reactions
- Asymmetric Synthesis and Catalysis
- Plant-Microbe Interactions and Immunity
- Organophosphorus compounds synthesis
- Cancer therapeutics and mechanisms
- Bioactive Compounds and Antitumor Agents
- Synthesis of heterocyclic compounds
- Molecular spectroscopy and chirality
- Marine Toxins and Detection Methods
- Alkaloids: synthesis and pharmacology
- Fluorine in Organic Chemistry
- Phytochemistry and Biological Activities
- Axial and Atropisomeric Chirality Synthesis
- Mass Spectrometry Techniques and Applications
Sanofi (Germany)
2014-2023
Sanofi (France)
2022
Imperial College London
2009-2014
Ludwig-Maximilians-Universität München
2006
Abstract Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of candidates their metabolites. Herein we report a photoredox‐initiated hydrogen atom transfer (HAT) protocol which efficiently selectively introduces deuterium or tritium at C(sp 3 )−H bonds, utilizing heavy water (D 2 O T O) isotope source, guanidine base. This has been successfully applied to incorporation...
With progress in genome sequencing and data sharing, 1,000s of bacterial genomes are publicly available. Genome mining-using bioinformatics tools terms biosynthetic gene cluster (BGC) identification, analysis, rating-has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing genetic potential phylum Bacteroidetes revealed Chitinophaga as most talented genus BGC abundance diversity. Guided by computational predictions, we...
It is shown that the marine key metabolite oroidin undergoes Diels-Alder reactions with electron-poor dienophiles. However, on heating of in absence any reaction partner, cyclization to natural product cyclooroidin takes place. This first direct conversion another pyrrole-imidazole alkaloid.
Abstract Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease that can lead to irreversible cirrhosis and cancer. Early diagnosis NASH vital detect before it becomes life‐threatening, yet noninvasively differentiating from simple steatosis challenging. Herein, bifunctional probes have been developed target the hepatocyte‐specific asialoglycoprotein receptor (ASGPR), expression which decreases during progression. The results show allow longitudinal,...
Herein, we describe the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. The linear peptide structure contains an unprecedented (2R,3S)-γ-N-methyl-β-hydroxy-histidine moiety. exhibits anti-Gram-negative activity against Escherichia coli (E. coli) and is taken up via two transporter systems, SbmA YejABEF. Furthermore, biosynthetic gene cluster (BGC) was identified a biosynthesis model proposed involving 12-modular non-ribosomal synthetase/polyketide synthase....
After the first total synthesis combined with structure revision, we performed thorough in vitro and vivo profiling of underexplored tetrapeptide GE81112A. From determination biological activity spectrum physicochemical early absorption-distribution-metabolism-excretion-toxicity (eADMET) properties, as well data regarding tolerability pharmacokinetics (PK) mice efficacy an Escherichia coli-induced septicemia model, were able to identify critical limiting parameters original hit compound....
The onset temperature of the retro-Diels−Alder reactions diketo-1,3-dioxin-2-ones to generate α,γ,ε-triketo-ketenes was found be significantly reduced with 2-phenyl substitution. These ketenes, generated at 78 °C, were trapped alcohols provide resorcylate esters following aromatization by sequential reaction cesium acetate and trifluoroacetic acid. methodology applied iteratively total synthesis antibiotics W1278A, -B, -C. It is noteworthy that in this process linking monomer units occurs...
Abstract The total synthesis of the naturally occurring antibiotic GE81112A, a densely functionalized tetrapeptide, is reported. Comparison spectral data with those natural product and lack biological activity synthesized compound led us to revise published configuration 3‐hydroxypipecolic acid moiety. This hypothesis was fully validated by corresponding epimer.
A visible light-mediated photocatalyzed C–C-bond benzylic functionalization of phenolic ether-containing drug-like compounds is presented.
Abstract Studies towards the total synthesis of natural product radicicol are described that employ a late‐stage esterification and aromatization by trapping ketene intermediate. The subsequent biomimetic resultant triketo ester gave highly functionalized resorcylates. Two distinct methods were examined trap intermediate through either an intermolecular or intramolecular process. In first approach, resorcylate was followed ring‐closing metathesis, which macrolactone protected precursors to...
Abstract With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining – using bioinformatics tools terms biosynthetic gene cluster (BGC) identification, analysis rating has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing genetic potential phylum Bacteroidetes revealed Chitinophaga as most talented genus BGC abundance diversity. Guided by computational predictions, we...
Tuberculosis represents one of the ten most common courses death worldwide and emergence multidrug-resistant M. tuberculosis makes discovery novel anti-tuberculosis active structures an urgent priority. Here, we show that (+)-floyocidin B representing first example a dihydroisoquinoline class fungus-derived natural products, displays promising antitubercular hit properties. (+)-Floyocidin was identified by activity-guided extract screening its structure unambiguously determined total...
A convenient protocol for the preparation of 4(5)-acyl-2-aminoimidazoles and vinylogues is disclosed employing a crystalline imidazole-derived iminophosphorane as coupling partner in Heck Sonogashira reactions. For first time, derivatives urocanic acid bearing free amino group 2′-position are described.
Abstract Die erste Totalsynthese des antibiotisch wirksamen Naturstoffs GE81112A, eines hoch funktionalisierten Tetrapeptids, wurde abgeschlossen. Der Vergleich der NMR‐Daten und biologischen Aktivität synthetischen Verbindung mit den Daten für Naturstoff führte zur Korrektur publizierten absoluten Konfiguration stereogenen Zentrums 3‐Hydroxypipecolinsäure‐Einheit Synthese biologisch aktiven GE81112A korrekten Konfiguration.
All four possible stereoisomers of the natural product (−)-avicennone C were synthesized using two different methods for ring closure. The absolute stereochemistry was elucidated unambiguously by comparison analytical data with those reported and single X-ray crystal diffraction synthetic intermediates. proposed structure needed to be revised regard configuration stereogenic center bearing secondary hydroxyl group. synthesis offers a flexible, selective, efficient access all may value...
The GE81112 series, consisting of three naturally occurring tetrapeptides and synthetic derivatives, is evaluated as a potential lead structure for the development new antibacterial drug. Although first total synthesis GE81112A reported by our group provided sufficient amounts material an initial in depth biological profiling compound, improvements routes toward key building blocks were needed further upscaling structure–activity relationship studies. major challenges identified poor...
The recently discovered natural product (NP) (+)-floyocidin B with antimicrobial activity against Mycobacterium tuberculosis displays a hitherto unknown dihydroisoquinolinone scaffold in the class of epoxyquinone NPs. 4,5-regioselective functionalization 2-chloropyridines was identified as suitable strategy leading to total syntheses and analogs. In this paper, we present long winding evolution process final synthetic pathway, including model systems for route scouting elucidation side...
Abstract Visible light mediated late-stage functionalization is a rising field in synthetic and medicinal chemistry, allowing the fast diversified modification of valuable, potentially therapeutic compounds such as peptides. However, there are relatively few mild methodologies for C(sp 3 )-H complex Herein, we report visible photocatalytic protocol benzylic C-H tyrosine related bonds. The embraced radical-cation/deprotonation strategy enables an incorporation wide range valuable functional...