A5004462569- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Click Chemistry and Applications
- Cyclization and Aryne Chemistry
- Catalytic Alkyne Reactions
- RNA and protein synthesis mechanisms
- Carbohydrate Chemistry and Synthesis
- RNA modifications and cancer
- Oxidative Organic Chemistry Reactions
- Genomics and Phylogenetic Studies
- Cancer Treatment and Pharmacology
- Bacterial Genetics and Biotechnology
- Inhalation and Respiratory Drug Delivery
- Pharmacological Effects and Assays
- Advanced biosensing and bioanalysis techniques
- Chemical synthesis and alkaloids
- Asthma and respiratory diseases
- RNA Interference and Gene Delivery
- Neurological diseases and metabolism
- Fluorine in Organic Chemistry
- Bacteriophages and microbial interactions
- Biotin and Related Studies
- Catalytic C–H Functionalization Methods
Novartis (United States)
2018-2020
Harvard University
2011-2013
ETH Zurich
2010-2012
Swiss Tropical and Public Health Institute
2007
University of Würzburg
2007
This Minireview highlights recent advances in the field of aryne and cyclohexyne chemistry that have allowed extraordinary reactivity these entities to be harnessed during course natural product syntheses. The syntheses presented rely on use reactive species chemoselective transformations follow unprecedented synthetic strategies are inspiring for practitioners organic chemistry.
Abstract Dieser Kurzaufsatz stellt neueste Fortschritte auf dem Gebiet der Arin‐ und Cyclohexinchemie vor, die es ermöglicht haben, außergewöhnliche Reaktivität dieser Verbindungen in Naturstoffsynthese nutzbar zu machen. Die vorgestellten Synthesen beruhen Nutzung reaktiven Spezies chemoselektiven Umsetzungen, folgen noch nicht dagewesenen Synthesestrategien sind daher inspririerend für organische Synthesechemie.
The cycloinsertion of cyclohexyne into a pentalene has provided access to the carbon scaffold guanacastepenes in nine steps. A late-stage diversifying oxidation core structure enabled synthesis guanacastepene N and first total O. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: publisher is responsible for content functionality any...
New antibiotic drugs need to be identified address rapidly developing resistance of bacterial pathogens common antibiotics. The natural moenomycin A is the prototype for compounds that bind peptidoglycan glycosyltransferases (PGTs) and inhibit cell wall biosynthesis, but it cannot used as a drug. Here we report chemoenzymatic synthesis fluorescently labeled, truncated analogue based on minimal pharmacophore. This probe, which has optimized enzyme binding properties compared moenomycin, was...
Abstract The synthesis of SCF 3 as well SeCF isosteres two OCF ‐containing drugs was achieved through visible light and copper‐catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical ADME properties without introducing intrinsic liabilities. groups are more lipophilic than their oxygen counterpart; however, microsomal stability is unchanged, indicating these molecular changes may be beneficial for in vivo half‐life. Enabled by modern synthetic methods,...
Cyclohexyne steps into the ring! is used for facile synthesis of polycyclic, medium sized rings. Its insertion cyclic ketones enables rapid access to densely functionalized building blocks. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The publisher responsible content functionality any supporting information supplied Any queries...
Advances in the design of permeable peptides and synthesis large arrays macrocyclic with diverse amino acids have evolved on parallel but independent tracks. Less precedent combines their respective attributes, thereby limiting potential to identify peptide ligands for key targets. Herein, we present novel 6-, 7-, 8-mer cyclic (MW 774–1076 g·mol–1) passive permeability oral exposure that feature thioether ring-closing common array formats, including DNA- RNA-templated synthesis. Each herein,...
Abstract Diversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting the elucidation of novel biological mechanisms. In parallel development DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient identify protein binders. Despite recent advancements this field, most DEL syntheses are limited by presence sensitive DNA-based constructs. Here, we describe design, synthesis, and...
Abstract The guanacastepenes are a family of 15 diterpenes that share common 5‐6‐7 tricyclic core, which is decorated with quaternary centers, unsaturation, hydroxyl and carbonyl groups. Some these natural products show interesting antimicrobial potency. Their collective structural biological features have stirred up vibrant activity among organic chemists. Herein, we disclose an account our studies toward the synthesis number guanacastepenes. synthetic strategy relies on use cyclohexyne in...
Cyclohexin steigt in den Ring! Unter Verwendung von wurden auf einfache Weise Polycyclen mit mittelgroßen Ringen synthetisiert. Die Insertion cyclische Ketone eröffnet einen schnellen Zugang zu Bausteinen hoher Funktionalisierungsdichte. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by the authors. Please note: The publisher is responsible for content...
Functionalization of RNA at the 5'-terminus is important for analytical and therapeutic purposes. Currently, these RNAs are synthesized de novo starting with a chemically functionalized 5'-nucleotide, which incorporated into using chemical synthesis or biochemical techniques. Methods direct modification native would provide an attractive alternative but currently underexplored. Herein, we report that diazo compounds can be used to selectively alkylate 5'-phosphate ribo(oligo)nucleotides give...
Abstract Cystine-knot peptides (CKPs) are naturally occurring that exhibit exceptional chemical and proteolytic stability. We leveraged the CKP carboxypeptidase A1 inhibitor as a scaffold to construct phage-displayed libraries subsequently screened these collections against HTRA1, trimeric serine protease implicated in age-related macular degeneration osteoarthritis. The initial hits were optimized by using affinity maturation strategies yield highly selective potent picomolar inhibitors of...
The naphthylisoquinoline (NIQ) alkaloids from tropical Ancistrocladaceae and Dioncophyllaceae plants show high antiplasmodial activities in vitro vivo, even against chloroquine-resistant strains of the malaria pathogen. For directed optimization these activities, an investigation mode action seems most rewarding. We have therefore embarked on identification respective target protein Plasmodium falciparum. this purpose, we developed a flexible pathway for synthesis chemically divergent series...
Die Cycloinsertion von Cyclohexin in ein Pentalen ermöglichte den Zugang zum Guanacastepen-Kohlenstoffgerüst lediglich neun Stufen. Durch eine diversifizierende Oxidation des Grundgerüsts zu einem späten Zeitpunkt gelangen die Synthese Guanacastepen N und erste Totalsynthese O. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by the authors. Please note:...
Abstract Functionalization of RNA at the 5′‐terminus is important for analytical and therapeutic purposes. Currently, these RNAs are synthesized de novo starting with a chemically functionalized 5′‐nucleotide, which incorporated into using chemical synthesis or biochemical techniques. Methods direct modification native would provide an attractive alternative but currently underexplored. Herein, we report that diazo compounds can be used to selectively alkylate 5′‐phosphate...
Introduction Inhaled drugs offer advantages for the treatment of respiratory diseases over oral by delivering drug directly to lung, thus improving therapeutic index. There is an unmet medical need novel therapies lung diseases, exacerbated a multitude challenges design inhaled small molecule drugs.