A5074010625- Asymmetric Hydrogenation and Catalysis
- Crystallization and Solubility Studies
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Analysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Catalytic Cross-Coupling Reactions
- Analytical Chemistry and Chromatography
- Organometallic Complex Synthesis and Catalysis
- Marine Sponges and Natural Products
- Cyclopropane Reaction Mechanisms
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
- Drug Solubulity and Delivery Systems
- Synthetic Organic Chemistry Methods
- Advanced Chemical Sensor Technologies
- Protein purification and stability
- Optimal Experimental Design Methods
- Antibiotics Pharmacokinetics and Efficacy
- Fluid Dynamics and Mixing
- Coordination Chemistry and Organometallics
- Carbohydrate Chemistry and Synthesis
- Industrial Vision Systems and Defect Detection
- Analytical Methods in Pharmaceuticals
- Cancer therapeutics and mechanisms
- Process Optimization and Integration
GlaxoSmithKline (United Kingdom)
2005-2023
Age UK
2016-2023
GlaxoSmithKline (Netherlands)
2022
GlaxoSmithKline (United States)
2017
University of Bristol
2001-2012
Imperial College London
2006
University of Oxford
2005
Université de Montpellier
2003
A Design of Experiment (DoE) and kinetic screening study was carried out using an automated reaction platform, as a case study, early stage in the synthesis late phase developmental candidate investigated. Key impurities were tracked kinetically modeled, significant factors impacting impurity formation identified. In particular, that influence diastereomer 4, precursor to API identified Critical Quality Attribute (CQA), optimized minimize its formation. Acetic acid, methanesulfonic volumes...
Non-contact computer vision complements traditional offline sampling methods for catalytic reaction monitoring.
The ligand, P(o-tolyl)3, is ubiquitous in applied synthetic chemistry and catalysis, particularly Pd-catalyzed processes, which typically include Pd(OAc)2 (most commonly used as Pd3(OAc)6) a precatalyst. Herrmann–Beller palladacycle [Pd(C^P)(μ2-OAc)]2 (where C^P = monocyclopalladated P(o-tolyl)3) easily formed from reaction of with P(o-tolyl)3. mechanisms by this precatalyst system operates are inherently complex, studies previously implicating Pd nanoparticles (PdNPs) reservoirs for active...
An even-handed approach: by use of an enantiomerically enriched substrate and study the changes in enantiomer ratio under pseudo zero-order conditions, racemic catalysts may be employed to determine whether pure catalyst would effective for kinetic resolution (see scheme; E=CO2 Me).
A conceptually novel approach to hetero Diels-Alder adducts of carbonyl compounds is described using as the key steps an antibody-mediated kinetic resolution hydroxyenones followed by a ring-closure process. Various beta-hydroxyenones proved be very good substrates for antibodies 84G3- and 93F3-catalyzed retro-aldol reactions, allowing preparation highly enantiomerically enriched (up 99% ee) precursors pyranones. An attractive feature this methodology possibility convert these...
This work provides simulations as well experimental results from kinetic resolutions to demonstrate that a constant product enantioselectivity versus conversion profile in resolution is not general consequence of pseudo zero order kinetics [substrate] but occurs only under specific mechanistic constraints. For such be observed, the reaction must follow mechanism exhibiting saturation for one enantiomeric on two parallel pathways. single catalyst species, this will limited situations...
We report a computer vision strategy for the extraction and colorimetric analysis of catalyst degradation product formation kinetics from video footage. The palladium(II) pre-catalyst systems to form ‘Pd black’ is investigated as widely relevant case study catalysis materials chemistries. Beyond catalysts in isolation, investigation Pd-catalyzed Miyaura borylation reactions revealed informative correlations between colour parameters (most notably ΔE, colour-agnostic measure contrast change)...
Eine Methode zur Vorhersage, ob ein enantiomerenreiner Katalysator für eine kinetische Racematspaltung prinzipiell geeignet ist, wird vorgestellt: Dafür wurde nicht racemisches, sondern enantiomerenangereichertes Substrat eingesetzt (siehe Schema; E=CO2Me) und unter Bedingungen einer Reaktionskinetik pseudo-nullter Ordnung das Enantiomerenverhältnis des Substrats geändert.
Asymmetric catalysis is predominantly associated with the use of enantiomerically pure chiral ligands and catalysts. Although racemic catalysts have been employed quite extensively in polymerization, their utility mainstream organic synthesis catalyst development has arguably rather overlooked. This Minireview collates various themes for strategic application catalysts, ranging from estimation selectivity determination enantiomeric excess, through to control regio- stereochemical outcomes,...
A new and improved synthetic route to an intermediate in the synthesis of phosphinate ester GSK2248761A is described. In key step, we describe first process-scale example a palladium-catalyzed phosphorus–carbon coupling give entire backbone one telescoped stage 65% average yield on 68 kg scale. This unusual chemistry enabled be reduced from six stages four eliminated number environmentally unfriendly reagents solvents.
Disproportionation is a major issue in formulations containing salts of weakly basic drugs. Despite considerable interest risk assessment approaches for disproportionation, the prediction salt-to-base conversion remains challenging. Recent studies have highlighted several confounding factors other than pHmax that appear to play an important role salt disproportionation and suggested kinetic barriers need be considered addition thermodynamic driving force when assessing undergo parent free...
The commercially available reagent trimethylsilyldiazomethane [1] can be used as a stable and safe alternative to diazomethane in one-carbon homologations, the Arndt-Eistert reaction, [2] homologation of carbonyl compounds [3] [4] O-methylation carboxylic acids, phenols alcohols. Additionally, serve C-N-N synthon for preparation azoles.
The development of the synthetic process to PPAR-α receptor antagonist 5-((4-(tert-butoxy)-3-methylphenoxy)methyl)-3-(4-(tert-butyl)phenyl)-1,2,4-oxadiazole (GW641597X) 1 is described. discussion ranges from initial supply route, used deliver early batches for preliminary safety studies enable dosing in man, an efficient manufacturing which delivered 35 kg drug substance following on a pilot plant campaign. includes key oxidative Baeyer–Villiger reaction, where identified sodium perborate...
The rate of reaction between N, N'-dicyclohexylbarbituric acid 1 and ethyl 2-isocyanatoacetate 2 is invariant with temperature. Positive orders in each reactant dissociation triethylammonium salts product 3 at elevated temperature indicate that occurs via a catalytic mechanism where changes to the positions equilibria negate turnover-limiting step. A model for consumption flow reactor accurately predicted outcome laboratory-scale multivariate study.
The Herrmann-Beller catalyst, Pd[(C^P)(μ
Abstract Die asymmetrische Katalyse ist in erster Linie mit der Anwendung von enantiomerenreinen chiralen Liganden und Katalysatoren verbunden. Obwohl racemische chirale relativ großem Umfang Polymerisationen eingesetzt wurden, blieben sie organischen Synthese Katalysatorentwicklung bisher weitgehend außen vor. Dieser Kurzaufsatz trägt verschiedene Aspekte strategischen racemischen zusammen, angefangen Abschätzung ihrer Selektivität Bestimmung des Enantiomerenüberschusses, über die regio‐...
Amidation of indole 2-carboxylate 1 with ammonia gas via the imidazolide 2 gave GSK2248761A API 3, which was in development for treatment HIV. Three significant impurities, namely phosphinic acid 4, N-acyl urea 8, and indoloyl carboxamide 6, were formed during reaction, original process unable to produce within clinical specification when run at scale. Investigation into origin, fate, control these impurities led a new able specification.
Abstract Review: about 60 refs.