A5049922312- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Synthesis and Catalysis
- Asymmetric Hydrogenation and Catalysis
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Nanomaterials for catalytic reactions
- Click Chemistry and Applications
- Fluorine in Organic Chemistry
- Folate and B Vitamins Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Catalytic C–H Functionalization Methods
- Molecular spectroscopy and chirality
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Catalysis for Biomass Conversion
- Biochemical and Molecular Research
- Antimicrobial Peptides and Activities
- Catalysis and Hydrodesulfurization Studies
- Advanced Synthetic Organic Chemistry
- Cancer Research and Treatments
- Synthesis and pharmacology of benzodiazepine derivatives
Helmholtz Institute for Pharmaceutical Research Saarland
2019-2025
Helmholtz Centre for Infection Research
2019-2025
German Center for Infection Research
2019-2025
Global Antibiotic Research & Development Partnership
2024
University of Groningen
2016-2019
Saarland University
2019
University of Pisa
2010-2016
Institute of Molecular Science and Technologies
2014-2016
Institute for the Chemistry of OrganoMetallic Compounds
2012-2014
Catalytic asymmetric conjugate addition reactions represent a powerful strategy to access chiral molecules in contemporary organic synthesis. However, their applicability conjugated alkenyl-N-heteroaromatic compounds, of particular interest medicinal chemistry, has lagged behind applications other substrates. We report highly enantioselective and chemoselective catalytic transformation wide range β-substituted alkenyl-N-heteroaromatics corresponding alkylated products. This operationally...
Radical copolymerisation of divinylbenzene and a properly modified enantiomerically pure imidazolidinone inside stainless steel column in the presence dodecanol toluene as porogens afforded first example chiral organocatalyst immobilized onto monolithic reactor. Organocatalyzed cycloadditions between cyclopentadiene cinnamic aldehyde were performed under continuous-flow conditions; by optimizing experimental set up, excellent enantioselectivities (90% ee at 25 °C) high productivities (higher...
General methods to prepare chiral pyridine derivatives are greatly sought after due their significance in medicinal chemistry. Here, we report highly enantioselective catalytic transformations of poorly reactive β-substituted alkenyl pyridines access a wide range alkylated pyridines. The simple methodology involves reactivity enhancement via Lewis acid (LA) activation, the use readily available and Grignard reagents, copper-chiral diphosphine ligand catalyst. Apart from allowing introduction...
Abstract The ubiquitous opportunistic pathogen Pseudomonas aeruginosa is responsible for severe infections and notoriously known acquiring antimicrobial resistance. Inhibiting the bacterium's extracellular elastase, LasB – a zinc‐dependent protease presents promising strategy to mitigate its virulence. Within this medicinal chemistry–driven hit‐to‐lead optimization campaign, new series of highly potent dipeptidic phosphonates designed synthesized following structure–based drug‐discovery...
Target-directed dynamic combinatorial chemistry (tdDCC) enables identification, as well optimization of ligands for un(der)explored targets such the anti-infective target 1-deoxy-d-xylulose-5-phosphate synthase (DXPS). We report use tdDCC to first identify and subsequently optimize binders/inhibitors DXPS. The initial hits were also optimized their antibacterial activity against E. coli M. tuberculosis during subsequent runs. Using tdDCC, we able generate acylhydrazone-based inhibitors...
Nearly quantitative yields and high enantiomeric purity (89–95% ee) were attained in the course of 100 reaction cycles a polystyrene resin-supported Cinchona alkaloid organocatalyst enantioselective α-amination 2-oxindoles with diethyl azodicarboxylate. The catalytic material proved stable for >5300 h operation time over 8 months.
Single site OH → F substitution at the termini of maltotetraose leads to significantly improved hydrolytic stability towards α-amylase and α-glucosidase relative natural compound. To explore effect molecular editing, selectively modified oligosaccharides were prepared via a convergent α-selective strategy. Incubation experiments in purified α-glucosidase, human murine blood serum, provide insight into influence fluorine on these clinically important scaffolds. Enhancements ca. 1 order...
Abstract Fluorinated motifs have a venerable history in drug discovery, but as C(sp 3 )−F‐rich 3D scaffolds appear with increasing frequency, the effect of multiple bioisosteric changes on molecular recognition requires elucidation. Herein we demonstrate that installation 1,3,5‐stereotriad, substrate for commonly used lipase from Pseudomonas fluorescens does not inhibit recognition, inverts stereoselectivity. This provides facile access to optically active, stereochemically well‐defined...
Abstract α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient scarce. In particular, the α-chiral with challenging tetrasubstituted carbon stereocentre is a long-standing problem catalytic additions organometallic reagents to ketimines that would give direct access these molecules underdeveloped. Here we report highly enantioselective N -sulfonyl protected silyl via addition inexpensive, easy handle...
Abstract Inexpensive and readily available organomagnesium reagents were used for the catalytic enantioselective alkylation of enolizable N ‐sulfonyl ketimines. The low reactivity competing enolization ketimines was overcome by use a copper–phosphine chiral catalyst, which also rendered transformation highly chemoselective broad range ketimine substrates.
RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on as a hit identification strategy. Upon design of N-acylhydrazone-based libraries, showed clear templating effect, amplifying 19 N-acylhydrazones. Screening against RAD51-BRCA2 protein-protein interaction via ELISA assay...
Even with the aid of available methods, configurational assignment natural products can be a challenging task that is prone to errors, and it sometimes needs corrected after total synthesis or single-crystal X-ray diffraction (XRD) analysis. Herein, absolute configuration amidochelocardin revised using combination XRD, NMR spectroscopy, experimental ECD spectra, time-dependent density-functional theory (TDDFT)-ECD calculations. As was obtained via biosynthetic engineering chelocardin, we...
Abstract The straightforward synthesis of polystyrene‐supported Chinchona alkaloids and their application in the asymmetric dimerization ketenes is reported. Six different immobilized derivatives, consisting three dimeric two monomeric 9‐ O ethers, were prepared by “click” anchoring soluble alkaloid precursors on to azidomethyl resins. resulting insoluble polymer‐bound (IPB) organocatalysts employed for promoting in‐situ generated ketenes. After opening ketene dimer intermediates with N ,...
Matrix metalloproteinases (MMPs) are involved in a spectrum of physiological processes, rendering them attractive targets for small-molecule drug discovery. Strategies to achieve selective inhibition continue be intensively pursued, facilitated by advances structural biology. Herein, we harness MMPs 2, 8, 9, and 13 validate the vicinal difluoro motif as hybrid bioisostere CF3 Et (BITE) series modified barbiturate inhibitors. Crystallographic analyses representative structures reveal...
Abstract A convenient route for the covalent immobilization of quinidine and hydroquinidine pyridazine ethers on insoluble polystyrene supports is described, which avoids need chromatographic purifications at any stage. The use heterogeneized alkaloid derivatives in asymmetric organocatalytic dimerization ketenes afforded high enantioselectivity values (90–97% ee ) course 20 reaction cycles.
Abstract A straightforward procedure is presented for the covalentimmobilization of ester and silyl ether derivatives Cinchona alkaloid 10,11‐dihydroquinidine within insoluble cross‐linked silicone elastomeric films. These materials were effective heterogeneous organocatalysts in asymmetric dimerization ketenes, which provided chiral Weinreb β‐ketoamides 28–83 % yield 79–99 ee course several recycles. productivity/enantioselectivity protocol also proposed to better assess relative merits...
Abstract The enantioselective organocatalytic methanolysis of cis ‐1,2,3,6‐tetrahydrophthalic anhydride mediated by quinidine derivatives with pyridazine or anthraquinone core was investigated, carrying out a detailed nuclear magnetic resonance study the conformational preferences alkaloid catalysts in pure solvent and presence reaction substrates products. No significant interaction between meso ‐anhydride detected. In contrast, evidence for considerable influence alcohol reactant on state...
We present a study on sequential conjugate addition of Grignard reagents to alkenyl-heteroarenes followed by trapping the resulting enolates, yielding moderate good diastereoselectivities. Contrary conventional wisdom, one-pot addition/trapping using two reactive Michael acceptors in combination with Grignard can proceed via least acceptor. This unusual chemoselectivity is triggered presence Lewis acid, reverting usual reactivity order acceptors.
Abstract Inexpensive and readily available organomagnesium reagents were used for the catalytic enantioselective alkylation of enolizable N ‐sulfonyl ketimines. The low reactivity competing enolization ketimines was overcome by use a copper–phosphine chiral catalyst, which also rendered transformation highly chemoselective broad range ketimine substrates.