Roger M. Howard
Pfizer
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Publication
Featured researches published by Roger M. Howard.
Green Chemistry | 2011
S. van Pelt; R. L. M. Teeuwen; Michiel Janssen; Roger A. Sheldon; Peter J. Dunn; Roger M. Howard; R. Kumar; I. Martínez; J. W. Wong
The use of Pseudomonas stutzerilipase (PSL) as a biocatalyst for aminolysis reactions with bulky substrates has been investigated. PSL compared favorably to Novozym® 435 (immobilized Candida antarcticalipase B, NOV435) in the aminolysis of various bulky methyl esters and amines. While NOV435 demonstrated a higher rate of aminolysis with methyl 2-phenylpropionic acid as the acyl donor, PSL outperformed NOV435 with secondary amines as the nucleophile. Methanol inhibition and a low affinity for bulky acyl donors were found to be the two main reasons for relatively low rates in the PSL-catalyzed aminolysis reactions. It was demonstrated that the use of molsieve 4A had a significant effect on the aminolysis rate and amide yield, since it enabled the effective removal of the inhibiting methanol from the reaction mixture.
Green Chemistry | 2012
Georges Assaf; Graham Checksfield; Doug Critcher; Peter J. Dunn; Stuart Field; Laurence James Harris; Roger M. Howard; Gemma Scotney; Adam Scott; Suju Mathew; Geoffrey M. H. Walker; Alexander Wilder
The Pfizer Green Chemistry metrics program is described and exemplified with a case history involving the synthesis of (S,S)-reboxetine succinate. The initial route used a classical resolution approach and generated high levels of waste. This route was replaced by an enantiospecific synthesis which used Sharpless epoxidation chemistry, an enzymatic process to selectively protect a primary alcohol and a new efficient method of chiral morpholine construction as key steps. These improvements reduced the levels of waste produced by the synthesis by more than 90%. Detailed metrics starting from a common starting material (trans-cinnamyl alcohol) for all routes of synthesis are presented.
Green Chemistry | 2011
Matthew Badland; Michael Paul Burns; Robert Carroll; Roger M. Howard; Daniel Laity; Nathan J. Wymer
Chemoenzymatic syntheses of two key intermediates in the preparation of a potent β-3 receptor agonist 1 are described. A lipase-catalysed hydrolytic desymmetrisation is employed in a new synthesis of intermediate 7, which avoids the use of alkyl-tin reagents. A second biotransformation delivers chiral chlorohydrin 5 from its parent ketone in greater enantiomeric excess than the previously-described Noyori-reduction process. A brief discussion of the enantioselectivity of a set of single-point mutants of Sporobolomyces salmonicoloraldehyde reductase in this bioreduction is also presented.
Chemcatchem | 2018
Roger M. Howard; Jeremy Steflik; Nicholas J. Weise; Juan Mangas-Sanchez; Sarah L. Montgomery; Robert Crook; Rajesh Kumar; Nicholas J. Turner
Reductive amination of carbonyl compounds constitutes one of the most efficient ways to rapidly construct chiral and achiral amine frameworks. Imine reductase (IRED) biocatalysts represent a versatile family of enzymes for amine synthesis through NADPH‐mediated imine reduction. The reductive aminases (RedAms) are a subfamily of IREDs that were recently shown to catalyze imine formation as well as imine reduction. Herein, a diverse library of novel enzymes were expressed and screened as cell‐free lysates for their ability to facilitate reductive amination to expand the known suite of biocatalysts for this transformation and to identify more enzymes with potential industrial applications. A range of ketones and amines were examined, and enzymes were identified that were capable of accepting benzylamine, pyrrolidine, ammonia, and aniline. Amine equivalents as low as 2.5 were employed to afford up to >99 % conversion, and for chiral products, up to >98 % ee could be achieved. Preparative‐scale reactions were conducted with low amine equivalents (1.5 or 2.0) of methylamine, allylamine, and pyrrolidine, achieving up to >99 % conversion and 76 % yield.
Angewandte Chemie | 2017
Godwin A. Aleku; Mahima Sharma; Juan Mangas-Sanchez; Roger M. Howard; Jeremy Steflik; Rajesh Kumar; Ralph W. Adams; Iustina Slabu; Robert Crook; Gideon Grogan; Timothy W. Wallace; Nicholas J. Turner
Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and ω-transaminase (ω-TA) biocatalysts to establish the key stereocentres of these molecules. Several enantiocomplementary IREDs were identified for the synthesis of (R)- and (S)-5-methyl-6,7-dihydro-5H-dibenz[c,e]azepine with excellent enantioselectivity, by reduction of the parent imines. Crystallographic evidence suggests that IREDs may be able to bind one conformer of the imine substrate such that, upon reduction, the major product conformer is generated directly. ω-TA biocatalysts were also successfully employed for the production of enantiopure 1-(2-bromophenyl)ethan-1-amine, thus enabling an orthogonal route for the installation of chirality into dibenz[c,e]azepine framework.
ACS Catalysis | 2016
Shahed Hussain; Andy Hill; Lorna J. Hepworth; Roger M. Howard; Keith Raymond Mulholland; Sabine L. Flitsch; Nicholas J. Turner
Tetrahedron-asymmetry | 2013
Andrew S. Rowan; Thomas S. Moody; Roger M. Howard; Toby J. Underwood; Iain Miskelly; Yanan He; Bo Wang
Organic Process Research & Development | 2011
Stewart T. Hayes; Georges Assaf; Graham Checksfield; Chi Cheung; Doug Critcher; Laurence James Harris; Roger M. Howard; Suju Mathew; Christian T. Regius; Gemma Scotney; Adam Scott
Organic Process Research & Development | 2011
Kenneth J. Butcher; Steven M. Denton; Stuart Field; Adam T. Gillmore; Gareth W. Harbottle; Roger M. Howard; Daniel Laity; Christian J. Ngono; Benjamin A. Pibworth
Organic Process Research & Development | 2011
Céline Praquin; Pieter D. de Koning; Philip Peach; Roger M. Howard; Sarah L. Spencer