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Mikael Widersten - One of the best experts on this subject based on the ideXlab platform.
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Substrate‐dependent hysteretic behavior in StEH1‐catalyzed hydrolysis of styrene Oxide derivatives
The FEBS journal, 2008Co-Authors: Diana Lindberg, Adolf Gogoll, Mikael WiderstenAbstract:The substrate selectivity and enantioselectivity of Solanum tuberosum epOxide hydrolase 1 (StEH1) have been explored by steady-state and pre-steady-state measurements on a series of styrene Oxide derivatives. A preference for the (S)- or (S,S)-enantiomers of styrene Oxide, 2-methylstyrene Oxide and Trans-Stilbene Oxide was established, with E-values of 43, 160 and 2.9, respectively. Monitoring of the pre-steady-state phase of the reaction with (S,S)-2-methylstyrene Oxide revealed two observed rates for alkylenzyme formation. The slower of these rates showed a negative substrate concentration dependence, as did the rate of alkylenzyme formation in the reaction with the (R,R)-enantiomer. Such kinetic behavior is indicative of an additional, off-pathway step in the mechanism, referred to as hysteresis. On the basis of these data, a kinetic mechanism that explains the kinetic behavior with all tested substrates Transformed by this enzyme is proposed. Regioselectivity of StEH1 in the catalyzed hydrolysis of 2-methylstyrene Oxide was determined by (13)C-NMR spectroscopy of (18)O-labeled diol products. The (S,S)-enantiomer is attacked exclusively at the C-1 epOxide carbon, whereas the (R,R)-enantiomer is attacked at either position at a ratio of 65 : 35 in favor of the C-1 carbon. On the basis of the results, we conclude that differences in efficiency in stabilization of the alkylenzyme intermediates by StEH1 are important for enantioselectivity with styrene Oxide or Trans-Stilbene Oxide as substrate. With 2-methylstyrene Oxide, slow conformational changes in the enzyme also influence the catalytic efficiency.
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Implications for an ionized alkyl-enzyme intermediate during StEH1-catalyzed Trans-Stilbene Oxide hydrolysis.
Biochemistry, 2006Co-Authors: Lisa T. Elfström, Mikael WiderstenAbstract:The catalytic mechanism of epOxide hydrolase (EC 3.3.2.3) involves acid-assisted ring opening of the oxirane during the alkylation half-reaction of hydrolysis. Two tyrosyl residues in the active site of epOxide hydrolases have been shown to contribute to the catalysis of enzyme alkylation, but their mechanism of action has not been fully described. We have investigated the involvement of the active site Tyr154 and Tyr235 during S,S-Trans-Stilbene Oxide hydrolysis catalyzed by potato epOxide hydrolase StEH1. Tyr phenol ionizations of unliganded enzyme as well as under pre-steady-state conditions during catalysis were studied by direct absorption spectroscopy. A Transient UV absorption, indicative of tyrosinate formation, was detected during the lifetime of the alkyl-enzyme intermediate. The apparent pKa of Tyr ionization was 7.3, a value more than 3 pH units below the estimated pKa of protein Tyr residues in the unliganded enzyme. In addition, the pH dependencies of microscopic kinetic rates of catalyzed S...
Patrick Metzner - One of the best experts on this subject based on the ideXlab platform.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of organic chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:[reaction: see text] A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20-10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of Organic Chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20−10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
Marion Davoust - One of the best experts on this subject based on the ideXlab platform.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of organic chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:[reaction: see text] A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20-10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of Organic Chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20−10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
Jean-françois Brière - One of the best experts on this subject based on the ideXlab platform.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of organic chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:[reaction: see text] A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20-10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of Organic Chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20−10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
Paul-alain Jaffrès - One of the best experts on this subject based on the ideXlab platform.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of organic chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:[reaction: see text] A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20-10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.
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Design of Sulfides with a Locked Conformation as Promoters of Catalytic and Asymmetric Sulfonium Ylide Epoxidation
The Journal of Organic Chemistry, 2005Co-Authors: Marion Davoust, Jean-françois Brière, Paul-alain Jaffrès, Patrick MetznerAbstract:A new generation of 2,5-dimethylthiolanes with a locked conformation was developed to promote the asymmetric addition of chiral sulfonium ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis of Trans-Stilbene Oxide derivatives with enantiomeric ratios ranging from 95:5 to 98:2. This user-friendly organocatalytic process proved to be efficient with 20−10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide intermediate conformation is given on the basis of a computational ab initio study.