A5025547024- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Synthetic Organic Chemistry Methods
- Advanced Synthetic Organic Chemistry
- Chemical synthesis and alkaloids
- Microbial Natural Products and Biosynthesis
- Asymmetric Synthesis and Catalysis
- PARP inhibition in cancer therapy
- Carbohydrate Chemistry and Synthesis
- DNA Repair Mechanisms
- Chemical Synthesis and Analysis
- Cell death mechanisms and regulation
- Alkaloids: synthesis and pharmacology
- Virus-based gene therapy research
- Cancer therapeutics and mechanisms
- Bioactive Compounds and Antitumor Agents
- Microtubule and mitosis dynamics
- Synthesis and Biological Activity
- Inflammatory mediators and NSAID effects
- Electron Spin Resonance Studies
- Inflammasome and immune disorders
- Synthesis and pharmacology of benzodiazepine derivatives
- Phosphorus compounds and reactions
- Cyclopropane Reaction Mechanisms
Université de Montréal
2011-2016
3M (United States)
2011-2016
DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor human Polθ (encoded by POLQ). A high-throughput screening campaign 350,000 compounds identified 11 micromolar hit, giving rise the N2-substituted fused pyrazolo series, which was validated biophysical methods. Structure-based design...
Lest we forget: 50 years after pactamycin was first isolated from a fermentation broth of Streptomyces pactum var pactum, this highly functionalized aminocyclopentitol natural product has finally succumbed to total synthesis. The modular and stereocontrolled introduction functional groups should lead the synthesis less toxic congeners that maintain antibacterial cytotoxic activities. Among plethora microbial secondary metabolites produced by soil bacterium family is pactamycin, structurally...
Abstract Anhand zwölf repräsentativer Beispiele stellen wir in diesem Aufsatz Strategien für die Totalsynthese komplexer Naturstoffe vor, zwei oder mehr benachbarte stereogene quartäre Kohlenstoffatomen ihren komplexen Molekülstrukturen enthalten. Das Hauptaugenmerk liegt dabei auf den Methoden zur Konstruktion quartärer stereogener Kohlenstoffzentren, einschließlich der Synthese desselben Naturstoffs verschiedenen Wegen durch unterschiedliche Forschergruppen; dies soll Vielfalt...
ATR is a key kinase in the DNA-damage response (DDR) that synthetic lethal with several other DDR proteins, making it an attractive target for treatment of genetically selected solid tumors. Herein we describe discovery novel inhibitor guided by pharmacophore model to position hydrogen bond. Optimization was driven potency and selectivity over related mTOR, resulting identification camonsertib (RP-3500) high excellent ADME properties. Preclinical evaluation focused on impact...
Cyclic GMP-AMP synthase (cGAS) is an intracellular sensor of double-stranded DNA that triggers a pro-inflammatory response upon binding. The interest in cGAS as drug discovery target has increased substantially over the past decade due to growing evidence linking its activation numerous peripheral and neurological diseases. Here, we report binding mode previously described inhibitors while also uncovering structural basis for interspecies potency shifts within this chemotype. A single...
This article describes synthetic studies that culminated in the first total synthesis of pactamycin and pactamycate and, parallel, two known congeners, de-6-MSA-pactamycin de-6-MSA-pactamycate, lacking 6-methylsalicylyl moiety. Starting with l-threonine as a chiron, series stereocontrolled condensations led to key cyclopentenone harboring spirocyclic oxazoline. A systematic functionalizations initially incorrect cyclopentanone epoxide, which was "inverted" under solvolytic conditions....
The tetracyclic core of daphniglaucin C was prepared from the known 4-keto-N-Boc methyl-l-prolinate in 15 steps with a cumulative yield 14.7%. key toward this motif feature reductive double bond transposition an unactivated tertiary allylic alcohol, Pd-catalyzed Stille coupling, and Dieckmann cyclizations.
The first total synthesis of the enantiomer indolizidine alkaloid, cyclizidine, was accomplished from readily available d-serine as starting chiron. relevant key reactions involve stereocontrolled construction ring system with required functionality and further elaboration to install cyclopropyl dienyl side chain. With this synthesis, absolute configuration natural product based on a redetermination its X-ray structure has been confirmed.
Biosynthetically and chemically derived analogs of the antibiotic pactamycin de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal antitumor drugs. Here, we report a 3.1-Å crystal structure de-6-MSA-pactamycin bound to its target site on Thermus thermophilus 30S ribosomal subunit. Although lacks MSA moiety, it shares same binding induces displacement nucleic acid template at E-site 30S. The highlights unique interactions between this analog ribosome,...
Mit leichter Verzögerung: 50 Jahre nach der ersten Isolierung von Pactamycin aus Fermentationsbrühe Streptomyces pactum var gelang endlich die Totalsynthese dieses hoch funktionalisierten natürlichen Aminocyclopentitols. Das modulare Einbringen funktionellen Gruppen sollte Synthese weniger toxischer Analoga ermöglichen, weiterhin antibakteriell und cytotoxisch wirken.
ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTSynthesis of a Model Tetracyclic Core Structure Calyciphylline B-Type AlkaloidsAmit Kumar Chattopadhyay, Helge Menz, Vu Linh Ly, Stéphane Dorich, and Stephen Hanessian*View Author Information Department Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montreal, QC, H3C 3J7, Canada*E-mail: [email protected]Cite this: J. Org. Chem. 2016, 81, 5, 2182–2188Publication Date (Web):February 15, 2016Publication History Received22 December...
Although the [2,3]-Wittig and Wittig-Still rearrangements have long been known, their application in generation of quaternary carbon centers carbocyclic ring systems is sparse. Model studies utilizing this strategy possible mechanisms are discussed herein. Unprecedented examples an α-elimination pathway from stannylmethyl allyl ethers as a major undesired product some reported.
Functionalized octahydroindoles were synthesized from (±)-cyclohex-2-en-1-ol as potential intermediates for convergent syntheses of several alkaloids plants the <i>Daphnyphyllum </i>genus.
<p>Supplementary Methods, Tables, Figures and References</p>
Abstract A variety of octahydroindole compounds are prepared via key intermediate (IV), which is synthesized from racemic cyclohex‐2‐en‐1‐ol.
Abstract Benzyl ether group is not suitable substrate for the present synthesis because of deprotection or decomposition substrate.
Abstract Review: [158 refs.