A5011388653- Chemical Reactions and Isotopes
- Asymmetric Hydrogenation and Catalysis
- Fluorine in Organic Chemistry
- Amino Acid Enzymes and Metabolism
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Mass Spectrometry Techniques and Applications
- Coordination Chemistry and Organometallics
- Chemical Synthesis and Characterization
- Boron Compounds in Chemistry
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Ammonia Synthesis and Nitrogen Reduction
- Muon and positron interactions and applications
- Radiopharmaceutical Chemistry and Applications
- Chemical Synthesis and Analysis
- Pharmacogenetics and Drug Metabolism
- Catalytic Alkyne Reactions
- Cancer therapeutics and mechanisms
- Radical Photochemical Reactions
- Drug Transport and Resistance Mechanisms
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Chemical Reaction Mechanisms
- Advanced Synthetic Organic Chemistry
Sanofi (Germany)
2016-2025
Doylestown Hospital
2024
ORCID
2020
University of Surrey
2016
Technische Universität Braunschweig
1998-2002
Queen's University
2001
Abstract This review addresses method developments both homogeneous and heterogeneous Pd‐ Pt‐catalyzed exchange, including catalyst activation principles recent practical applications together with example procedures. Specific requirements for isotopically labelled internal MS standard preparation are discussed from a Sanofi‐Aventis perspective on examples. Copyright © 2010 John Wiley & Sons, Ltd.
A novel and convenient protocol for the catalytic hydrogen-deuterium exchange of biologically active tertiary amines utilizing borrowing hydrogen methodology has been developed. In presence readily available Shvo catalyst, excellent chemoselectivity toward α- β-protons with respect to nitrogen atom as well high degree deuterium incorporation functional group tolerance is achieved. This allowed deuteration complex pharmaceutically interesting substrates, including examples actual marketed...
Abstract Wasserstoffisotope sind einzigartige Werkzeuge zur Identifizierung und Erforschung biologischer oder chemischer Vorgänge. Wasserstoffisotopenmarkierungen erlauben den spurlosen direkten Einbau einer zusätzlichen Masseneinheit eines radioaktiven Markers in ein organisches Molekül, dies praktisch ohne Änderungen der chemischen Struktur, physikalischen Eigenschaften biologischen Aktivität. Die Verwendung von deuteriummarkierten Isotopologen Untersuchung spezifischen...
For the first time, we describe highly selective homogeneous iridium-catalyzed hydrogen isotope exchange (HIE) of unactivated C(sp
Abstract Die steigende Nachfrage nach stabil isotopenmarkierten Verbindungen führt zu einem verstärkten Interesse an H/D‐Austauschreaktionen Kohlenstoffatomen. Heutzutage werden Deuterium‐markierte als interne Standards in der Massenspektrometrie eingesetzt oder helfen dabei, mechanistische Theorien untermauern. Der Zugang diesen deuterierten erfolgt über einen Austausch von Wasserstoff gegen Deuterium im Zielmolekül deutlich effizienter und preiswerter die klassische Synthese. Schwerpunkt...
Conventional thermal and microwave conditions were compared for hydrogen-deuterium (H/D) exchange reactions of aminobenzoic acids catalysed by NaBD(4)-activated Pd/C or RhCl(3) with D(2)O as the deuterium source. We also investigated different metal catalysts (including Pd/C, Pt/C) under an efficient H/D aromatic heterocyclic compounds. Even higher incorporations obtained Pt/C catalyst mixtures due to previously observed synergistic effect. Finally, we have applied these optimised one-step...
The first examples of selective ortho-directed C-H activation with unprotected 2-aryltetrazoles are described. A new base-assisted protocol for iridium(i) hydrogen isotope exchange catalysis allows access to ortho-deuterated and tritiated tetrazoles, including the tetrazole-containing pharmaceutical, Valsartan. Preliminary mechanistic studies also presented.
Abstract Die vielfältigen Anwendungen der Wasserstoffisotope (Deuterium, D, und Tritium, T) in den physikalischen Biowissenschaften erfordern unterschiedliche Methoden für deren Einführung verschiedenste molekulare Architekturen. In diesem Aufsatz beschreiben wir die neuesten Fortschritte bei synthetischen C‐H‐Funktionalisierung Wasserstoffisotopenaustausch.
The increasing demand for isotopically labeled compounds has provided an appreciable impetus the development of improved methods late-stage introduction isotopes hydrogen (deuterium or tritium). Moreover, sp3-rich molecules are becoming increasingly common in exploration chemical space drug design. Herein, we report efficient iridium(I)-catalyzed C–H activation method isotope exchange sp3 bonds. A wide range substrates have been labeled, including active pharmaceutical ingredients,...
The preparation of N-heterocyclic carbene-stabilized iridium nanoparticles and their application in hydrogen isotope exchange reactions is reported. These air-stable easy-to-handle showed a unique catalytic activity, allowing selective efficient incorporation on anilines using D2 or T2 as isotopic source. usefulness this transformation has been demonstrated by the deuterium tritium labeling diverse complex pharmaceuticals.
Site-selective incorporation of deuterium into biologically active compounds is high interest in pharmaceutical industry. We present a mild and environmentally benign metal-free method for the remote selective radical C-H monodeuteration aliphatic bonds various amides with inexpensive heavy water (D2 O) as source. The uses easily installed N-allylsulfonyl moiety an N-radical precursor that generates C-radical via site-selective 1,5- or 1,6-hydrogen atom transfer (HAT). Methyl thioglycolate,...
The selective activation of sp3 carbon–hydrogen bonds in the presence multiple C–H is challenging and remains supreme importance chemical research. Late-stage modification complex molecules via high prevalence organic synthesis. Herein, we describe a C(sp3)–H bond α-position to an amine carbanion intermediate. In several α-amine sites, only one specific position selectively activated. Applying this protocol, proposed intermediate was effectively trapped with different electrophiles such as...
Abstract Human glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation cancer cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, inhibitor-conjugated insulin being explored mitigate hypoglycemia side effect therapy in type 1 diabetes. Reasoning that exofacial GLUT1/3 may be favored therapeutic applications, we report here engineering a GLUT3...
Abstract Phenylene‐bridged hybrid phosphine‐imidazolin‐2‐imine R P,N R′ ligands (R=Ph, Cy, i‐ Pr, t‐ Bu; R′=Me, Pr) were prepared from 1,2‐dibromobenzene by palladium‐catalyzed C–N coupling with 1,3,4,5‐tetramethylimidazolin‐2‐imine or 1,3‐diisopropyl‐4,5‐dimethylimidazolin‐2‐imine, followed lithiation tert ‐butyllithium and reaction the chlorophosphines (R 2 PCl). Their dimeric iridium complex [Ir(cod)Cl] (cod=1,5‐cyclooctadiene) subsequent anion exchange sodium...
Abstract Well‐defined ruthenium(II) biscarboxylate complexes enabled selective ortho ‐deuteration with weakly‐coordinating, synthetically useful carboxylic acid outstanding levels of isotopic labeling. The robust nature the catalytic system was reflected by a broad functional group tolerance in an operationally‐simple manner, allowing isotope labeling challenging pharmaceuticals and bioactive heterocyclic motifs. synthetic power our method highlighted tritium‐labeling repaglinide,...
Abstract For the first time, a catalytic protocol for highly selective hydrogen isotope exchange (HIE) of phenylacetic acid esters and amides under very mild reaction conditions is reported. Using homogeneous iridium catalyst supported by bidentate phosphine‐imidazolin‐2‐imine P,N ligand, HIE on series derivatives proceeds with high yields, selectivity, deuterium incorporation up to 99 %. The method fully adaptable specific requirements tritium chemistry, its effectiveness was demonstrated...