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Roger A Sheldon

Publications and source records attributed to Roger A Sheldon.

17 recordsLinked to original sources
PubMed2005

Cross-linked aggregates of (R)-oxynitrilase: a stable, recyclable biocatalyst for enantioselective hydrocyanation.

[Reaction: see text] The (R)-oxynitrilase from almonds was immobilized as a cross-linked enzyme aggregate (CLEA) via precipitation with 1,2-dimethoxyethane and subsequent cross-linking using glutaraldehyde. The resulting preparation was a highly effective hydrocyanation catalyst under microaqueous conditions, which suppress the nonenzymatic background reaction. The beneficial effect of these latter conditions on the hydrocyanation of slow-reacting aldehydes is demonstrated. The oxynitrilase CLEA was recycled 10 times without loss of activity.

Aldehyde-Lyases↗
PubMed2005

The first enantioselective synthesis of the amavadin ligand and its complexation to vanadium.

The ligand of the naturally occurring vanadium compound amavadin found in Amanita muscaria, (2S, 2'S)-N-hydroxyimino-2,2'-dipropionic acid (1), was synthesized stereoselectively in two steps with 43% overall yield. After complexation of this ligand to vanadyl acetate, amavadin was isolated in quantitative yield. Due to the chirality at vanadium amavadin consists of a mixture of delta and lambda diastereoisomers. Directly after its synthesis, the delta to lambda ratio of amavadin is 2.27 and it decreases to 0.80 after equilibrium has been reached. During this epimerization the optical rotation for V[(2S,2'S)-N-hydroxyimino-(2,2')-dipropionate]2 (=amavadin) changes from [alpha](D)25 = +36 degrees to +114.0 degrees (c = 0.5, H2O). For V[(2R,2'R)-N-hydroxyimino-(2,2')-dipropionate] the optical rotation changes from [alpha](D)25 = -36 degrees to -113.2 degrees (c = 0.5, H2O).

Alanine↗
PubMed2004

Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous aluminosilicate: application and solvent effects.

A new Brønsted acidic aluminosilicate, AlTUD-1, with ideal characteristics for catalyst immobilisation (mesoporous structure, high surface area, and high Al(tetrahedral)/Si ratio), was used successfully for the noncovalent anchoring of two well-established asymmetric hydrogenation catalysts: [Rh(I)(cod)[(R,R)-MeDuPHOS]]BF4 (1) and [Rh(I)(cod)[(S,S)-DiPAMP]]BF4 (2). The new heterogeneous catalysts, 1-AlTUD-1 and 2-AlTUD-1, prepared by a straightforward ion-exchange procedure, were highly active and selective in the asymmetric reduction of dimethyl itaconate (3) and methyl 2-acetamidoacrylate (4), giving enantiomeric excesses of up to >98%. The catalysts showed similar behaviour to their homogeneous counterparts. Catalyst 2-AlTUD-1 could be re-used multiple times without loss of enantioselectivity or activity. Leaching of Rh showed a significant dependence on the polarity of the solvent in which the catalysis was performed. By applying tert-butylmethyl ether (MTBE) as solvent, the loss of Rh could be reduced to <0.1%. The solvent also had a noteworthy effect on the enantioselectivity in the hydrogenation of 4 (an effect not seen with 3 as substrate), that is, in MeOH the ee was 92%, in MTBE it dropped to 26% when using 2-AlTUD-1 as catalyst.

Aluminum Silicates↗
PubMed2004

Efficient immobilisation of Rh-MonoPhos on the aluminosilicate AlTUD-1.

Rhodium-MonoPhos was successfully immobilised by ionic interactions on aluminosilicate AlTUD-1. The resulting new heterogeneous catalyst can be used in water and showed excellent enantioselectivity and activity in the asymmetric hydrogenation of methyl-2-acetamidoacrylate.

Journal Article↗
PubMed2004

A new, mild cross-linking methodology to prepare cross-linked enzyme aggregates.

Cross-linked enzyme aggregates (CLEAs) were prepared from several enzymes (penicillin G acylase, hydroxynitrile lyase, alcohol dehydrogenase, and two different nitrilases) by precipitation and subsequent cross-linking using dextran polyaldehyde. In most cases, higher immobilization yields were obtained using the latter cross-linker as compared with the commonly used glutaraldehyde. Active site titration of penicillin acylase CLEAs showed that the higher activity originated from a significantly lower loss in active sites using dextran polyaldehyde as a cross-linking agent. It is proposed that macromolecular cross-linkers are too large to penetrate the protein active site and react with catalytically essential amino acid residues.

Binding Sites↗
PubMed2003

Crude aminoacylase from aspergillus sp. is a mixture of hydrolases.

A range of cross-linked enzyme aggregates (CLEAs) was prepared from commercially available aminoacylase I. Results from three test reactions showed that aminoacylase does not possess aminolysis or alcoholysis activity, both previously ascribed to this enzyme. This result was confirmed using aminoacylase purified by chromatographic techniques, which leads us to conclude that the previously observed acylations of esters and amines is due to other enzymes present as impurities in the crude aminoacylase I.

Acylation↗
PubMed2003

Cu(II)-nitroxyl radicals as catalytic galactose oxidase mimics.

Results from Hammett correlation studies and primary kinetic isotope effects for the CuCl-TEMPO catalysed aerobic benzyl alcohol oxidations are inconsistent with an oxoammonium based mechanism. We postulate a copper-mediated dehydrogenation mechanism, in which TEMPO regenerates the active Cu(II)-species. This mechanism is analogous to that observed for Galactose Oxidase and mimics thereof.

Alcohols↗
PubMed2003

Biocatalytic transformations in ionic liquids.

Room temperature ionic liquids are non-volatile, thermally stable and highly polar; they are also moderately hydrophilic solvents. Here, we discuss their use as reaction media for biocatalysis. Enzymes of widely diverging types are catalytically active in ionic liquids or aqueous biphasic ionic liquid systems. Lipases, in particular, maintain their activity in anhydrous ionic liquid media; the (enantio)selectivity and operational stability are often better than in traditional media. The unconventional solvent properties of ionic liquids have been exploited in biocatalyst recycling and product recovery schemes that are not feasible with traditional solvent systems.

Catalysis↗
PubMed2003

Immobilised enzymes: carrier-bound or carrier-free?

Recent advances have been made in the development of carrier-free immobilised enzymes and several criteria established for the selection of immobilised enzymes for biotransformations. The pros and cons of carrier-free versus carrier-bound immobilised enzymes and of each type of carrier-free enzyme are discussed.

Catalysis↗
PubMed2002

A two-step, one-pot enzymatic synthesis of cephalexin from D-phenylglycine nitrile.

A cascade of two enzymatic transformations is employed in a one-pot synthesis of cephalexin. The nitrile hydratase (from R. rhodochrous MAWE)-catalyzed hydration of D-phenylglycine nitrile to the corresponding amide was combined with the penicillin G acylase (penicillin amidohydrolase, E.C. 3.5.1.11)-catalyzed acylation of 7-ADCA with the in situ-formed amide to afford a two-step, one-pot synthesis of cephalexin. D-Phenylglycine nitrile appeared to have a remarkable selective inhibitory effect on the penicillin G acylase, resulting in a threefold increase in the synthesis/hydrolysis (S/H) ratio. 1,5-Dihydroxynaphthalene, when added to the reaction mixture, cocrystallized with cephalexin. The resulting low cephalexin concentration prevented its chemical as well as enzymatic degradation; cephalexin was obtained at 79% yield with an S/H ratio of 7.7.

Acetonitriles↗
PubMed2002

Active site titration as a tool for the evaluation of immobilization procedures of penicillin acylase.

Native and immobilized preparations of penicillin acylase from Escherichia coli and Alcaligenes faecalis were studied using an active site titration technique. Knowledge of the number of active sites allowed the calculation of the average turnover rate of the enzyme in the various preparations and allowed us to quantify the contribution of irreversible inactivation of the enzyme to the loss of catalytic activity during the immobilization procedure. In most cases a loss of active sites as well as a decrease of catalytic activity per active site (turnover rate) was observed upon immobilization. Immobilization techniques affected the enzymes differently. The effect of increased loading of penicillin acylase on the average turnover rate was determined by active site titration to assess diffusion limitations in the carrier.

Alcaligenes↗
PubMed2002

Penicillin acylase-catalyzed ampicillin synthesis using a pH gradient: a new approach to optimization.

The penicillin acylase-catalyzed synthesis of ampicillin by acyl transfer from D-(-)-phenylglycine amide (D-PGA) to 6-aminopenicillanic acid (6-APA) becomes more effective when a judiciously chosen pH gradient is applied in the course of the process. This reaction concept is based on two experimental observations: 1) The ratio of the initial synthesis and hydrolysis rates (V(S)/V(H)) is pH-dependent and exhibits a maximum at pH 6.5-7.0 for a saturated solution of 6-APA; 2) at a fixed 6-APA concentration below saturation, V(S)/V(H) increases with decreasing pH. Optimum synthetic efficiency could, therefore, be achieved by starting with a concentrated 6-APA solution at pH 7 and gradually decreasing the pH to 6.3 in the course of 6-APA consumption. A conversion of 96% of 6-APA and 71% of D-PGA into ampicillin was accomplished in an optimized procedure, which significantly exceeds the efficiency of enzymatic synthesis performed at a constant pH of either 7.0 or 6.3.

Ampicillin↗
PubMed2002

Evaluation of the performance of immobilized penicillin G acylase using active-site titration.

Penicillin G acylase from Escherichia coli was immobilized on Eupergit C with different enzyme loading. The activity of the immobilized preparations was assayed in the hydrolysis of penicillin G and was found to be much lower than would be expected on the basis of the residual enzyme activity in the immobilization supernatant. Active-site titration demonstrated that the immobilized enzyme molecules on average had turnover rates much lower than that of the dissolved enzyme. This was attributed to diffusion limitations of substrate and product inhibition. Indeed, when the immobilized preparations were crushed, the activity increased from 587 U g-1 to up to 974 U g-1. The immobilized preparations exhibited up to 15% lower turnover rates than the dissolved enzyme in cephalexin synthesis from 7-ADCA and D-(-)-phenylglycine amide. The synthesis over hydrolysis ratios of the immobilized preparations were also much lower than that of the dissolved enzyme. This was partly due to diffusion limitations but also to an intrinsic property of the immobilized enzyme because the synthesis over hydrolysis ratio of the crushed preparations was much lower than that of the dissolved enzyme.

Antigens, Neoplasm↗
PubMed2002

Selective ruthenium-catalyzed oxidation of 1,2:4,5-di-O-isopropylidene- beta-D-fructopyranose and other alcohols with NaOCl.

[reaction: see text] The asymmetric epoxidation catalyst 1,2:4,5-di-O-isopropylidene-beta-D-erythro-2,3-hexadiulo-2,6-pyranose 2 was obtained in high yield from 1,2:4,5-di-O-isopropylidene-beta-D-fructopyranose 1 via a recyclable ruthenium-catalyzed hypochlorite oxidation protocol under biphasic conditions (MTBE/water) in the presence of an alkaline buffer (pH 9.5). Other secondary alcohols were also oxidized selectively to the corresponding ketones.

Journal Article↗
PubMed2002

Green, catalytic oxidations of alcohols.

Three methods are described, in the context of the guiding principles of green chemistry, for the catalytic oxidation of alcohols. The first employs a recyclable oligomeric TEMPO catalyst (PIPO) and sodium hypochlorite as the oxidant in a bromide-free and chlorinated hydrocarbon solvent-free system. The second involves a ruthenium/TEMPO catalyst and oxygen as the oxidant. The third consists of a recyclable water-soluble palladium-diamine complex in conjunction with air as the oxidant in an aqueous biphasic system. The mechanisms of the ruthenium/TEMPO- and palladium-catalyzed oxidations are discussed, and the mechanism of the former is compared with that of the analogous copper/TEMPO catalyst.

Alcohols↗