A5050260763- Chemistry and Chemical Engineering
- Enzyme Catalysis and Immobilization
- Inorganic and Organometallic Chemistry
- Innovative Microfluidic and Catalytic Techniques Innovation
- Chemical Reaction Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Asymmetric Hydrogenation and Catalysis
- Chemical Reactions and Mechanisms
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Asymmetric Synthesis and Catalysis
- Steroid Chemistry and Biochemistry
- Process Optimization and Integration
- Synthesis and pharmacology of benzodiazepine derivatives
- Oxidative Organic Chemistry Reactions
- Fluorine in Organic Chemistry
- Synthesis and Reactions of Organic Compounds
- Organometallic Complex Synthesis and Catalysis
- Receptor Mechanisms and Signaling
- Nanomaterials for catalytic reactions
- Microbial Metabolism and Applications
- Synthesis and Reactivity of Heterocycles
- Synthesis and Characterization of Heterocyclic Compounds
Quorn (United Kingdom)
2012-2020
University of Nottingham
2010-2019
AstraZeneca (United Kingdom)
2006-2016
Loughborough University
2006-2016
AstraZeneca (Sweden)
2015
Södertälje Sjukhus
2015
AstraZeneca (United States)
2015
KTH Royal Institute of Technology
2015
University of Edinburgh
2013
Advanced Systems Technology (United States)
2009
In 2005, the ACS Green Chemistry Institute (GCI) and global pharmaceutical corporations developed GCI Pharmaceutical Roundtable to encourage integration of green chemistry engineering into industry. The has a list key research areas. purpose this perspective is summarise how that was agreed, provide an assessment current state art in those areas highlight for future improvement.
In 2005, the American Chemical Society (ACS) Green Chemistry Institute (GCI) and global pharmaceutical companies established ACS GCI Pharmaceutical Roundtable to encourage integration of green chemistry engineering into industry. The developed a list key research areas in 2007, which has served as guide for focusing research. Following that publication, have identified is intended be required companion first list. This publication summarizes process used identify agree on top describes these...
All this talk of water: Aqueous-based organocatalytic processes involve a complex set parameters, and holistic approach is the key to making informed decisions on benefits case-by-case basis. A fundamental mechanistic understanding role water in any reaction necessary before its general use reactions may be advocated. Copyright picture (water drops 1): Adam Hart-Davis.
Ecotoxicological tests, using OECD standard methods on some ionic liquids, have revealed that several very high toxicity towards freshwater algae and the invertebrate Daphnia magna (∼104−106 times more ecotoxic than methanol for worse cases). In addition these compounds show levels of to microorganisms responsible biodegradation in environment. These materials a significant potential damage aquatic ecosystem if released into water. We conclude considerable care should be exercised choice...
Enantiopure chiral amines synthesis using ω-transaminases is hindered by an unfavourable equilibrium, but when isopropylamine as the amine donor equilibrium can be completely displaced a specific dehydrogenase in situ for removal of formed acetone.
A survey of solvent usage for papers published in Organic Process Research & Development has been carried out the years 1997–2012. Three categories were studied: (i) solvents concern, (ii) dipolar aprotic solvents, and (iii) neoteric solvents. In analysis use it was found that nearly 50% DMF/DMAc/NMP/DMSO is attributed to nucleophilic substitution reactions (mostly SNAr SN2 reactions). Ideas on how minimise these four are presented, hoped ideas will be adopted by chemists looking at SN type...
Five gram negative and two positive bacterial strains known for their heavy metal tolerance or ability to reduce ions were coated with Pd(0) nanoparticles (NPs) via reduction of soluble Pd(II) under H2 following an initial uptake PdCl42- without added electron donor ('biosorption'), where the had a ~5-fold greater capacity Pd(II). Cupriavidis metallidurans accumulated exceptionally; possibility endogenous was not discounted. The rate subsequent H2-mediated correlated removed during...
Laccases are oxidase enzymes produced by 'white rot' fungi as part of a complex armoury redox used to break down lignin--part the carbon cycle nature. alone or in combination with co-catalysts have been shown oxidize xenobiotic compounds under conditions that can be described 'green'. This paper describes some novel oxidations using laccase-mediator method and current limitations use this technology.
A significant number of marketed pharmaceuticals contain active pharmaceutical ingredients that are manufactured in part using biocatalysis as a key enabling technology. The utilization is growing due to advances technologies for enzyme discovery, supply, and improvement, well an increased focus on applications chiral drugs green chemistry. Nevertheless, there still remains lack clarity around quality regulatory expectations when biotransformations research manufacturing, this can be barrier...
Wundermittel Wasser? Um entscheiden zu können, ob bei organokatalytischen Prozessen ein Zusatz von Wasser Vorteile mit sich bringt, ist stets die Gesamtbilanz des Verfahrens betrachten. Zudem bedarf es grundlegender Kenntnisse darüber, wie in Mechanismen chemischer Reaktionen eingreift, bevor sein genereller Einsatz befürwortet werden kann. Copyright für das Bild (water drops 1): Adam Hart-Davis.
ω-Transaminase enzyme chemistry provides an excellent methodology to build synthetically useful chiral amines from their corresponding ketones. An application of this methodology, providing a long-term commercial manufacturing route JAK2 kinase inhibitor, is reported herein.
Starting in 2007, the ACS Green Chemistry Institute Pharmaceutical Roundtable (GCIPR) has invested sustainable chemical reactions and technologies order to positively impact pharmaceutical manufacturing routes processes of future. It done so by committing over $2 million support a grant program focused on spurring innovative solutions industrially relevant problems with significant unmet need. This resulted funding 28 research programs from academic groups across globe, spanning wide range...
Laccases are oxidase enzymes produced by ‘white rot’ fungi as part of a complex armoury redox used to break down lignin – the carbon cycle nature. alone or in combination with co-catalysts have been shown oxidize xenobiotic compounds under conditions that can be described ‘green’. This paper describes some novel oxidations using laccase–mediator method and current limitations use this technology.
Screening of 60 transaminases using three different amine donors found that the ω-transaminase from Vibrio fluvialis together with (S)-α-methylbenzylamine to be most promising combination deliver desired (S)-1-(5-fluoropyrimidin-2-yl)-ethylamine (2) in almost quantitative conversion. The process was further improved by addition immiscible organic solvents toluene identified as suitable concerning distribution reactants without negatively impacting performance biocatalyst. Further...
Microbial ipso,ortho-dihydroxylation of benzoic acid by the B9 mutant strain Ralstonia eutropha permits rapid construction aminocyclitols containing a quaternary stereocentre. Installation amine functionality is achieved use an acylnitroso dienophile for hetero-Diels–Alder reaction. Both aminotetrols and aminohexols are accessible as single enantiomers this route. NOESY spectroscopic X-ray crystallographic analyses were required to distinguish cycloadduct isomers. Notably, subsequent...
A number of functional group reductions reported in the literature utilize mixtures triethoxysilane [(EtO3SiH)] and Lewis acids. It should be noted that this combination can produce highly pyrophoric toxic gas, silane (SiH4).
Using lipase catalysed, enzymatic esterification as a model reaction, we successfully demonstrate the use of miniaturized technology for biocatalytic reactions. Benchmarked against batch reactions, nine alkyl esters have been synthesized effectively, using Novozyme 435 in pressure driven, packed-bed, miniaturized, continuous flow reactor. In some cases close to 100% ester conversions were obtained. The paper also demonstrates ability screen enzyme substrate specificity.
The process development to the manufacturing route (2S)-7-([4,4'-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid hydrochloride (SB-214857-A, lotrafiban) is described. starting point previously reported intermediate (2RS)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic methyl ester. first stage a lipase-catalysed resolution of racemic ester (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic and subsequent...
An efficient synthesis of a 1,4-benzodiazepine was accomplished using copper catalysed amination an arylbromide with the soluble bis-tetrabutylammonium salt l-aspartic acid as key step.
Enantioselective oxidation of racemic O-methyl-N-hydroxycyclohexylethylamine, using a variant monoamine oxidase N (MAO-N) from Aspergillus niger, yields unreacted (R)-enantiomer (e.e. = 99%) together with the oxime exclusively in (E)-configuration.
A range of generic active pharmaceutical ingredients were examined for potential chiral alcohol motifs and derivatives within their structures that could be employed as key synthetic intermediates. For seven (APIs), eight precursor ketones acquired then subjected to reduction by >400 commercially available ketone reductases from different suppliers. Positive screening results achieved five screened, with multiple each successful ketone. Selectivity was typically >99.5% ee in most cases,...
Biocatalysis is essentially the use of enzymes to perform chemical transformations on organic compounds and has been exploited for applications in various industries including food, fine chemicals, agrochemicals, pharmaceuticals. Due their selectivity ability operate under mild conditions, offer clear advantages efficient sustainable manufacturing processes. Rapid development enabling technologies gene mining, molecular biology, biocatalyst evolution, bioprocess engineering, created...