- Chiral Pt/ZrO2 catalysts. enantioselective hydrogenation of 1-phenyl-1,2-propanedione
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The enantioselective hydrogenation of 1-phenyl-1,2-propanedione over Pt colloids stabilized with (R,S)-4,5-dihydro-4,5-diphenyl-2-(6-cyanopyridinyl) imidazoline (CI) supported on a meso-structured ZrO2 under a pressure of 40 bar of H2 at 298 K has been investigated. The metal loading in all catalysts was 1 wt%. The effect of the amount of chiral modifier on the metal particle size and on the catalytic behavior was analyzed. It was found that as the CI/Pt molar ratio increases from 2.5 to 3.5 the Pt crystal size decreases from 3.0 to 1.8 nm. All catalysts were very active in the studied reaction, with the most active one being the catalyst with smaller Pt particles, whereas the selectivity is higher in those catalysts with larger chiral modified Pt metal particles.
- Urbina, Claudia,Campos, Cristian,Pecchi, Gina,Claver, Carmen,Reyes, Patricio
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanodione on cinchonidine-modified Rh/MCM-41 catalysts
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Enantioselective hydrogenation of 1-phenyl-1,2-propanodione (PPD) on Rh/MCM-41 catalysts was studied. The catalysts were prepared using Rh(acac) 3 as a metal precursor and metal loadings that ranged from 0.5 to 1.5 wt%. The samples were characterised by nitrogen adsorption-desorption isotherms at 77 K using ICP-MS, XRD, TEM, XRD and XPS. The reaction was performed at 298 K, and 0.01 mol L-1 of PPD and cinchonidine (CD) was used as chiral modifier. The effect of the modifier concentration on the enantioselectivity (ee) and the conversion level in the hydrogenation reaction shows a relationship between the activity and ee as well as the CD concentration. The volcano-type curve observed for each catalyst suggests competitive adsorption of the modifier and substrate on the catalyst surface. The metal loading influences both the Rh crystallite size and catalytic behaviour. An increase in the Rh levels was accompanied by a parallel increase in both the crystallite size and number of Rh ensembles with a subsequent enhancement in both the conversion level and ee. The catalyst with the highest metal loading was 1.0 wt% Rh/MCM-41, and it displayed the highest ee among the catalysts studied. Additionally, the effects of hydrogen pressure and solvent nature on the catalytic activity were also studied. Moreover, the H2 pressure also influenced the conversion levels with only a minor effect on the ee values. Considering the solvent effects, we observed non-linear ee dependence with an increasing solvent dielectric constant, which showed a decrease in conversion levels in the order cyclohexane > toluene > tetrahydrofurane > dichloromethane.
- Torres, Cecilia C.,Campos, Cristian H.,Fierro,Reyes, Patricio,Ruiz, Doris
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanedione over Pt on immobilized cinchonidine on γ-Al2O3 catalysts
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Chirally modified γ-Al2O3 containing different amounts of cinchonidine were prepared by the chemical modification of cinchonidine with trimethoxysilane (TMS-CD). These solids were used as support of Pt catalysts containing 1 wt% Pt by chemical reduction of the hexachloroplatinic acid with H2 at 25°C and 40 bar. The characterization was carried out by elemental analysis of C, H and N, TG, DRIFT, NMR 13C and 29Si on solid state, N2 adsorption-desorption at 77 K, XDR, XPS and TEM. The catalytic activity was evaluated in the hydrogenation of 1-phenyl-propane-1,2-dione in a batch reactor at 298 K and 40 bar. The effect of H2 pressure, concentration substrate, catalyst mass, solvents effect and recycles, of the catalyst with the major enantiomeric excess was studied. It was found that all catalysts were active in the reaction being the enantiomeric excess of the target product, 1-R-phenyl-1-hydroxy-2-propanone in the range 30-44% and the best catalyst is that supported on γ-Al2O3 with a nominal content of 5 wt% TMS-CD. The results obtained in this study confirm that the variation of reaction conditions show a dependence on the activity and enantioselectivity for substrate adsorption in the metal active sites. In the solvent effect, enantiomeric excess decreased non-linearly with an increasing solvent dielectric and we could be attributed to the interactions between solvents and TMS-CD in the surface. In the recycles studies enantiomeric excess was achieved as 40% even after 3rd reuse with a slight loss in activity and enantiomeric excess.
- Campos, Cristian H.,Torres, Cecilia,Fierro, José L.G.,Reyes, Patricio
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanedione
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Enantioselective hydrogenation of a diketone, 1-phenyl-1,2-propanedione was studied in a pressurized reactor at 5 bar and at 0-25C in different solvents: ethanol, ethyl acetate, and dichloromethane over platinum catalysts. Both in situ modification (simultaneous addition of the reagent and the modifier) and pre-modification (preadsorption of the modifier prior to the reagent) of the catalyst were investigated using cinchonidine as catalyst modifier. Racemic hydrogenation proceeded with nearly the same rate as the selective hydrogenation in the presence of the catalyst modifier. The kinetic results revealed that the hydrogenation of the carbonyl group attached to the phenyl ring was preferred, the main product being 1-hydroxy-1-phenylpropanone; the ratio between 1-hydroxy-1-phenylpropanone and 2-hydroxy-1-phenylpropanone was about 11. The most effective and enantioselective catalyst was obtained by in situ modification in dichloromethane yielding in 67 mol% of (R)-1-hydroxy-1-phenylpropanone, corresponding to the enantiomeric excess of 64%. The enantiomeric excess was independent of the reactant conversion. In the second hydrogenation step the main product among diols was (1R,2S)-1-phenyl-1,2- propanediol.
- Toukoniitty, Esa,Maeki-Arvela, Paeivi,Kuzma, Marek,Villela, Alexandre,Kalantar Neyestanaki, Ahmad,Salmi, Tapio,Sjoeholm, Rainer,Leino, Reko,Laine, Ensio,Murzin, Dmitry Yu.
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanedione on immobilised cinchonidine-TiO2 catalysts
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The enantioselective hydrogenation of 1-phenyl-1,2-propanodione (PPD) was investigated using cinchonidine-immobilised Pt/TiO2 catalysts. Prior to metal deposition, TiO2 was chirally modified by the direct anchoring of cinchonidine (CD) using trimethoxysilane as coupling agent (TMS-CD). The catalysts were prepared using a high H2 pressure reduction-deposition method and were characterised by elemental analysis (C, H and N), TG, DRIFT, 13C and 29Si solid-state NMR, N 2 adsorption-desorption isotherms, XRD, XPS and HR-TEM. The catalytic activity was evaluated in a batch reactor at 298 K and 40 bar using cyclohexane as solvent with various cinchonidine concentrations. The results indicate that the enantioselectivity was sensitive to the CD surface concentration and the enantiomeric excess of the target product, 1-R-phenyl-1-hydroxy-2-propanone, was in the range of 25-51%. The best catalyst was the one supported on TiO 2 with a nominal content of 10 wt% TMS-CD. The effect of the H 2 pressure, the concentration of substrate, solvent and recyclability of the catalyst were studied. The results obtained confirmed that the variation of reaction conditions affects both the activity and enantioselectivity due to the substrate adsorption on the metal active sites. Concerning the solvent effect, the enantiomeric excess decreased non-linearly upon increasing the solvent dielectric constant; this was attributed to the interactions between solvents and TMS-CD on the surface. In the catalyst recycling studies, the enantiomeric excess decreased up to 40% after the 3rd reuse. The drop of activity and enantiomeric excess was attributed to the hydrogenation of the immobilised CD.
- Campos, Cristian H.,Torres, Cecilia C.,Dongil, Ana B.,Ruiz, Doris,Fierro, José L.G.,Reyes, Patricio
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanodione on Pt/ ZrO 2 catalysts
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The enantioselective hydrogenation of 1-phenyl-1,2-propanedione at 298K and pressure of 40 bar of H2 over zirconia supported Pt catalysts has been studied. Three different zirconia were prepared: i) ZrO2- P obtained by a precipitation procedure from ZrOCl2 ii) MSZrO 2 obtained by a sol-gel procedure using cetryltrimethylammonium bromide (CTMABR) as surfactant to get a mesostructured solid iii) CNTsZrO 2 obtained after impregnation of carbon nanotubes with ZrO(NO) 3 followed by pyrolisis and calcination. Pt (1wt%) was introduced on the support by impregnation of an aqueous solution of H2PtCl 6. The catalysts were characterized by nitrogen adsorption-desorption isotherms at 77 K, hydrogen chemisorption, XRD and TEM techniques. The reactions were carried out in a stainless steel batch reactor using cyclohexane as solvent and cinchonidine as chiral modifier. The presence of CD in the reaction medium is necessary to induce an enantiomeric excess (ee) of the desired product R-1phenyl-1 hydroxi-2-propanone. In all the studied systems, the relation between the enantioselectivity and the CD concentration added in situ exhibits a bell type curve; indicative of the importance of competitive adsorption between the modifier and the substrate on the catalyst surface. On the other hand, confinement effect led to an important enhancement in the activity in those catalysts supported on mesostructured supports, mainly in the Pt/CNTsZrO2 catalyst.
- Urbina, Claudia,Pecchi, Gina,Campos, Cristian,Reyes, Patricio
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- Enantioselective hydrogenation of 1-phenyl-propane-1,2-dione on immobilised cinchonidine Pt/SiO2 catalysts
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Chirally modified SiO2 containing different amounts of cinchonidine was prepared by the chemical modification of cinchonidine (CD) with trimethoxysilane over SiO2 that had been chemically activated with 1,4-dioxane/HCl. This solid wa
- Campos, Cristian H.,Oportus, Marcelo,Torres, Cecilia,Urbina, Claudia,Fierro, José L.G.,Reyes, Patricio
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- Whole-Cell Biocatalysis in Seawater: New Halotolerant Yeast Strains for the Regio- and Stereoselectivity Reduction of 1-Phenylpropane-1,2-Dione in Saline-Rich Media
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The application of green chemistry concepts in catalysis has considerably increased in recent years, and the interest in using sustainable solvents in the chemical industry is growing. One of the recent proposals to fall in line with this is to employ seawater as a solvent in biocatalytic processes. This involves selecting halotolerant strains capable of carrying out chemical conversions in the presence of the salt concentrations found in this solution. Recent studies by our group have revealed the interest in using strains belonging to Debaryomyces and Schwanniomyces for catalytic processes run in this medium. In the present work, we select other yeasts based on their halotolerance to widen the scope of this strategy. We consider them for the monoreduction of 1-phenylpropane-1,2-dione, a well-characterized reaction that produces acyloin intermediates of pharmaceutical interest. The results obtained herein indicate that using seawater as a solvent for this reaction is possible. The best ones were obtained for Saccharomyces cerevisiae FY86 and Kluyveromyces marxianus, for which acyloins with different stereochemistry were obtained with good to excellent enantiomeric excess.
- Andreu, Cecilia,del Olmo, Marcellí
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- Branched-chain keto acid decarboxylase from Lactococcus lactis (KdcA), a valuable thiamine diphosphate-dependent enzyme for asymmetric C - C bond formation
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The thiamine diphosphate-dependent, branched-chain 2-keto acid decarboxylase from Lactococcus lactis sup. cremoris Bl157 (KdcA) is a new valuable enzyme for the synthesis of chiral 2-hydroxy ketones. The gene was cloned and the enzyme was expressed as an
- Gocke, Doerte,Nguyen, Cong Luan,Pohl, Martina,Stillger, Thomas,Walter, Lydia,Mueller, Michael
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- Hydrogenation of 1-phenyl-1,2-propanedione over Pt catalysts modified by cinchona alkaloid O-ethers and the kinetic resolution of the 1-hydroxyketones generated
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Nine cinchona alkaloid O-ethers together with cinchonidine and cinchonine were studied as chiral modifiers in the enantioselective hydrogenation of 1-phenyl-1,2-propanedione over Pt/Al2O3. The influence of the O-substituent on the reaction rate, selectivity and product distribution was investigated. Apparent rate constants for all hydrogenation steps were calculated using a first-order kinetic approach resulting in a good agreement between the experimentally recorded and predicted concentrations. The experimentally observed structure-selectivity effects indicate that the mechanisms of enantiodifferentiation over the catalyst modified by parent cinchona alkaloids and their ether derivatives differ from each other. Moreover, the modifier structure-selectivity dependence and the solvent effect were different for enantio- and diastereoselection in the 1-phenyl-1,2-propanedione and 1-hydroxyketone hydrogenations. Correlation between the modifier substituent bulkiness and diastereoselectivity of the 1-hydroxyketone hydrogenation was observed. Data on the inversion of enantioselectivity of 1-phenyl-1,2-propanedione hydrogenation, diastereoselectivity and the sense of kinetic resolution of the 1-hydroxyketones were presented. Due to the complexity of the reaction network, several competing mechanistic pathways may be present in a single reaction system.
- Busygin, Igor,Waerna, Johan,Toukoniitty, Esa,Murzin, Dmitry Yu.,Leino, Reko
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- A combined experimental and theoretical study of 1-phenylpropane-1,2-dione hydrogenation over heterogeneous cinchonidine-modified Pt catalyst
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The enantioselective hydrogenation of vicinal diketones over cinchonidine-modified Pt resulted in enantiomeric excess of structurally similar (R)-enantiomers. Furthermore, the kinetic resolution was caused due to faster reaction of (S)-hydroxyketone further to diols, resulting in an increase of ee. The diastereoselectivities in diols were similar. The (R,S) or (S,R) diols were always the main products whereas considerably less (R,R) of (S,S) were formed. For the first time in 1-phenylpropane-1,2-dione (A) hydrogenation enantiomeric excesses of both C1O1 and C2O2 group have been reported. The ee1-OH and ee2-OH were 50 and 25%, respectively, at 50% conversion of A. Based on batch and continuous reactor experiments it could be concluded that the source of enantioselectivity is an increased formation rate of (R)-enantiomer and decreased formation rate of (S)-enantiomer. Theoretical calculations revealed that in the substrate-modifier diastereomeric complex the reactant forms a nonplanar s-cis conformation and bonds to the protonated cinchonidine either via a bifurcated hydrogen bond or with two hydrogen bonds where the OH group is involved also. Optimized diastereomeric complexes were equal in energy. The calculated proton affinity of CD was high, 1000 kJmol-1, indicating that protonation is feasible under typical experimental conditions.
- Toukoniitty, Esa,Nieminen, Ville,Taskinen, Antti,Paeivaerinta, Juha,Hotokka, Matti,Murzin, Dmitry Yu.
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- A new non-cinchona chiral modifier immobilized on Pt/SiO2 catalysts for enantioselective heterogeneous hydrogenation
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Pt heterogeneous catalysts were prepared by the covalent immobilization of (4′R,5′S)-4′,5′-dihydro-4′,5′-diphenyl-2-(6-cyanopyridyl)imidazoline (PyIm) as the asymmetric modifier. These novel series of catalysts were studied in the 1-phenyl-1,2-propanodione (PPD) hydrogenation. The effects of the PyIm surface concentration, hydrogen pressure, solvent nature and recycles on the reaction were studied. These modified catalysts represent the first effective immobilized chiral non-Cinchona-type modifier of Pt for the enantioselective hydrogenation. The enantio-differentiation was attributed to the substrate-modifier interactions involving hydrogen bonding between the keto-carbonyl O atom and the NH moiety PyIm. The results confirmed that the variations in the H2 pressure and the solvent affect the activity and the enantioselectivity due to the substrate adsorption on the active sites of the metal. Additionally, this heterogeneous catalyst can be conveniently reused at least five times without loss of its catalytic efficiency, but the enantioselectivity decreased, which may be due to the leaching of the modifier.
- Campos, Cristian H.,Torres, Cecilia C.,Leyton, Ariel,Belmar, Julio,Mella, Claudio,Osorio-Vargas, Paula,Ruiz, Doris,Fierro, José L.G.,Reyes, Patricio
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- Stereo- and Regioselectivity in Catalyzed Transformation of a 1,2-Disubstituted Vicinal Diol and the Corresponding Diketone by Wild Type and Laboratory Evolved Alcohol Dehydrogenases
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ADH-A from Rhodococcus ruber DSM 44541 catalyzes the oxidation of (S)-1-phenylethanol 3000-fold more efficiently as compared with the 2-hydroxylated derivative (R)-phenylethane-1,2-diol. The enzyme is also highly selective for sec-alcohols with comparably low activities with the corresponding primary alcohols. When challenged with a substrate containing two secondary alcohols, such as 1-phenylpropane-(1R,2S)-diol, ADH-A favors the oxidation of the benzylic carbon of this alcohol. The catalytic efficiency, however, is modest in comparison to the activity with (S)-1-phenylethanol. To investigate the structural requirements for improved oxidation of vicinal diols, we conducted iterative saturation mutagenesis combined with activity screening. A first-generation variant, B1 (Y54G, L119Y) displays a 2-fold higher kcat value with 1-phenylpropane-(1R,2S)-diol and a shift in the cooperative behavior in alcohol binding, from negative in the wild type, to positive in B1, suggesting a shift from a less active enzyme form (T) in the wild type to a more active form (R) in the B1 variant. Also, the regiopreference changed to favor oxidation of C-2. A second-generation variant, B1F4 (F43T, Y54G, L119Y, F282W), shows further improvement in the turnover and regioselectivity in oxidation of 1-phenylpropane-(1R,2S)-diol. The crystal structures of the B1 and B1F4 variants describe the structural alterations to the active site, the most significant of which is a repositioning of a Tyr side-chain located distal to the coenzyme and the catalytic zinc ion. The links between the changes in structures and stereoselectivities are rationalized by molecular dynamics simulations of substrate binding at the respective active sites.
- Maurer, Dirk,Enugala, Thilak Reddy,Hamnevik, Emil,Bauer, Paul,Lüking, Malin,Petrovi?, Du?an,Hillier, Heidi,Kamerlin, Shina C. L.,Dobritzsch, Doreen,Widersten, Mikael
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- A One-Pot Two-Step Enzymatic Pathway for the Synthesis of Enantiomerically Enriched Vicinal Diols
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Enantiomerically enriched 1,2-diols are prominent compounds that find numerous applications in organic chemistry. They are privileged building blocks for the synthesis of APIs (Active Pharmaceutical Ingredients), broadly used as chiral ligands in asymmetric catalysis, and efficient auxiliaries employed to control the stereochemical outcome of total synthesis. Among the number of strategies developed for the preparation of these molecules, enzyme mediated reactions have gained a crucial role in the toolbox of organic chemists for their high efficiency and sustainability. Herein we describe a one-pot two-step protocol designed by combining a thiamine diphosphate (ThDP)-dependent lyase and a NADH-dependent reductase. The ThDP-dependent acetoin:dichlorophenolindophenol oxidoreductase (Ao : DCPIP OR) is exploited to produce enantioenriched α-hydroxyketones through the benzoin-type condensation of methylacetoin with either aldehydes or activated ketones. The enantioenriched α-hydroxyketones undergo the selective reduction into the corresponding 1,2-diols in the same reaction mixture due to the addition of NAD+ and of the NADH-dependent acetylacetoin reductase (AAR). Sodium formate was selected as the sacrificial reductive reactant to generate and recycle in situ the precious NADH by formate-dehydrogenase. Unprecedented reported details on the cloning and expression of the AAR are reported as well.
- Giovannini, Pier Paolo,Müller, Michel,Presini, Francesco,Baraldi, Serena,Ragno, Daniele,Di Carmine, Graziano,Jacoby, Christian,Bernacchia, Giovanni,Bortolini, Olga
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- INFLUENCE OF ENOLATE GEOMETRY AND STRUCTURE ON THE STEREOCHEMISTRY OF THE ASYMMETRIC OXIDATION OF PROCHIRAL KETONE ENOLATES TO OPTICALLY ACTIVE α-HYDROXY KETONES
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The stereoselectivity for the asymmetric oxidation of enolates to optically active α-hydroxy ketones using (+)-(camphorylsulphonyl)oxaziridine is dependent on the enolate substitution pattern, the solution structure of the enolate and to a lesser extent the enolate geometry.
- Davis, Franklin A.,Sheppard, Aurelia C.,Lal, G. Sankar
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- Synthesis with good enantiomeric excess of both enantiomers of α-ketols and acetolactates by two thiamin diphosphate-dependent decarboxylases
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In addition to the decarboxylation of 2-oxo acids, thiamin diphosphate (ThDP)-dependent decarboxylases/dehydrogenases can also carry out so-called carboligation reactions, where the central ThDP-bound enamine intermediate reacts with electrophilic substrates. For example, the enzyme yeast pyruvate decarboxylase (YPDC, from Saccharomyces cerevisiae) or the E1 subunit of the Escherichia coli pyruvate dehydrogenase complex (PDHc-E1) can produce acetoin and acetolactate, resulting from the reaction of the central thiamin diphosphate-bound enamine with acetaldehyde and pyruvate, respectively. Earlier, we had shown that some active center variants indeed prefer such a carboligase pathway to the usual one [Sergienko, Jordan, Biochemistry 40 (2001) 7369-7381; Nemeria et al., J. Biol. Chem. 280 (2005) 21,473-21,482]. Herein is reported detailed analysis of the stereoselectivity for forming the carboligase products acetoin, acetolactate, and phenylacetylcarbinol by the E477Q and D28A YPDC, and the E636A and E636Q PDHc-E1 active-center variants. Both pyruvate and β-hydroxypyruvate were used as substrates and the enantiomeric excess was analyzed by a combination of NMR, circular dichroism and chiral-column gas chromatographic methods. Remarkably, the two enzymes produced a high enantiomeric excess of the opposite enantiomer of both acetoin-derived and acetolactate-derived products, strongly suggesting that the facial selectivity for the electrophile in the carboligation is different in the two enzymes. The different stereoselectivities exhibited by the two enzymes could be utilized in the chiral synthesis of important intermediates.
- Baykal, Ahmet,Chakraborty, Sumit,Dodoo, Afua,Jordan, Frank
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- Immobilised chiral inducer on Pt-based mesoporous titanate nanotubes as heterogeneous catalysts for enantioselective hydrogenation
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A new series of chiral porous titanate nanotubes (TNTs) containing (-)-11-trimethoxysilyl-cinchonidine (TMS-CD) moieties were synthesized via direct surface anchorage. These hybrid solids were used as supports for Pt (1 wt%) catalysts and evaluated in heterogeneous enantioselective hydrogenation of 1-phenyl-1,2-propanodione. The supports and catalysts were characterized by a variety of techniques including TGA, N2 adsorption isotherms, solid state NMR (13C and 29Si), XRD, HR-TEM, DRIFTs and XPS. For the best system the hydrogen pressure, solvent effects and recycles were studied. The maximum enantiomeric excess (ee) and the turnover frequency obtained under optimized conditions with 1% Pt/TNT-CD were 37% (at 15 wt% nominal content of TMS-CD) and 165 min-1 (at 10 wt% nominal content of TMS-CD), respectively. The variation of H2 pressure and solvent affects both the activity and enantioselectivity due to the substrate adsorption on the metal active sites. Additionally, these heterogeneous catalysts can also be easily recycled and reused for three times without the loss of activity and enantioselectivity. After the 3rd cycle, catalyst deactivation due to the leaching of Pt nanoparticles and modifier hydrogenation in the feed was detected.
- Campos, Cristian H.,Torres, Cecilia C.,Osorio-Vargas, Paula,Mella, Claudio,Belmar, Julio,Ruiz, Doris,Fierro, José L.G.,Reyes, Patricio
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- Silica supported rhodium metal nanoparticles stabilized with (-)-DIOP. Effect of ligand concentration and metal loading on the enantioselective hydrogenation of ketones
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Supported nanoparticles (NPs) in presence of chiral ligand (L) were synthesized for their use in enantioselective hydrogenation reactions. Catalysts were obtained by chemical reduction from rhodium chloride hydrate, RhCl 3×3H2O, in presence of (-)-DIOP ligand ((4R,5R)-4,5-Bis(diphenylphosphino-methyl)- 2,2-dimethyl-1,3-dioxolane) that allows to control NPs growing and to obtain solids having chiral surfaces. Chirally stabilized rhodium NPs on SiO2 were characterized using techniques such as: TEM, electron diffraction, EDS, nitrogen adsorption-desorption isotherms and XPS. This work includes the study of some variables such as metal loading and ligand concentration and their effect in metal core sizes, catalytic activity and enantioselectivity. Catalysts properties have also been evaluated in the hydrogenation of substrates: acetophenone (AP), 1-phenyl-1,2-propanedione (PPD), 3,4-hexanedione (HD), 2,3-butanedione (BD) and ethyl pyruvate (EP) as reaction test. Ligand plays a fundamental role in the synthesis of NPs and enantioselectivity in hydrogenations reactions. That is, due to it generates metal particle size 5.8 nm compared with unstabilized systems that generate average diameter around 14 nm. Results indicate increased activity in catalytic systems obtained from the stabilization of NPs. Enantioselectivity levels reach values up to 53% due to the chiral ligand is on the catalysts surface.
- Ruiz, Doris,Mella, Claudio,Fierro, Jose L.G.,Reyes, Patricio
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- Pyruvate Decarboxylase: a New Enzyme for the Production of Acyloins by Biotransformation
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Highly purified pyruvate decarboxylase from yeast has been shown to catalyse the condensation between pyruvate and a wide range of substituted benzaldehydes to give hydroxyketones (acyloins) of the same (R) enantiomeric series and of high optical purity,
- Kren, Vladimir,Crout, David H. G.,Dalton, Howard,Hutchinson, David W.,Koenig, Wilfred,et al.
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- NOVEL PROCESS FOR THE PREPARATION OF R-PHENYLACETYLCARBINOL AND β-AMINOALCOHOLS
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Disclosed herein is a process for the manufacture of (R)-phenylacetylcarbinol ((R)-PAC), (1R,2S). Ephedrine and its salts, (1R,2S)-norephedrine and its salts and 1-(Phenyl/Substituted phenyl)-2-(amino/alkylamino/dialklyamino) propan-1-ol and its salts, by enzymatic reduction of α-isonitrosopropiophenone (INP) and substituted α-isonitrosopropiophenone (substituted INP). The β-amino alcohols, produced by the process of present invention gives their corresponding diastereomers on Walden inversion. The present preparation process of (R)-PAC with (R)-PAC oxime as an intermediate has the advantage, that propiophenone as a key raw material which is easily available and has a low-price, operationally simple with high yield and a single process leading to the synthesis of several 1,2-aminoalcohol/ β- aminoalcohols active pharmaceutical ingredients. The design approach of the process is to reduce environmental impact of the product by comparing to the present manufacturing process.
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- Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716T butanediol dehydrogenase
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α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716T (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn2+ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.
- Bongaerts, Johannes,Jablonski, Melanie,Kipp, Carina Ronja,Molinnus, Denise,Muschallik, Lukas,Pohl, Martina,Sch?ning, Michael J.,Selmer, Thorsten,Siegert, Petra,Wagner, Torsten
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p. 12206 - 12216
(2020/04/20)
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- Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity
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The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.
- Shanati, Tarek,Lockie, Cameron,Beloti, Lilian,Grogan, Gideon,Ansorge-Schumacher, Marion B.
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p. 6202 - 6211
(2019/08/15)
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- Exploiting Cofactor Versatility to Convert a FAD-Dependent Baeyer–Villiger Monooxygenase into a Ketoreductase
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Cyclohexanone monooxygenases (CHMOs) show very high catalytic specificity for natural Baeyer–Villiger (BV) reactions and promiscuous reduction reactions have not been reported to date. Wild-type CHMO from Acinetobacter sp. NCIMB 9871 was found to possess an innate, promiscuous ability to reduce an aromatic α-keto ester, but with poor yield and stereoselectivity. Structure-guided, site-directed mutagenesis drastically improved the catalytic carbonyl-reduction activity (yield up to 99 %) and stereoselectivity (ee up to 99 %), thereby converting this CHMO into a ketoreductase, which can reduce a range of differently substituted aromatic α-keto esters. The improved, promiscuous reduction activity of the mutant enzyme in comparison to the wild-type enzyme results from a decrease in the distance between the carbonyl moiety of the substrate and the hydrogen atom on N5 of the reduced flavin adenine dinucleotide (FAD) cofactor, as confirmed using docking and molecular dynamics simulations.
- Xu, Jian,Peng, Yongzhen,Wang, Zhiguo,Hu, Yujing,Fan, Jiajie,Zheng, He,Lin, Xianfu,Wu, Qi
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supporting information
p. 14499 - 14503
(2019/09/17)
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- Immobilized chiral rhodium nanoparticles stabilized by chiral P-ligands as efficient catalysts for the enantioselective hydrogenation of 1-phenyl-1,2-propanedione
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This work reports the efficient synthesis of enantio-enriched alcohols by asymmetric hydrogenation of 1-phenyl-1,2-propanedione using chiral nanoparticles (NPs) supported on SiO2. The chiral catalysts were synthesized by reducing the [Rh(μ?OCH3)(C8H12)]2 precursor under H2 in the presence of P-chiral ligands as stabilizers and SiO2 as support. Synthesis of catalysts in mild conditions was performed from labile organometallic precursor and chiral ligands provided small and well defined chiral nanoparticles (≤ 3 nm). The catalysts were characterized by XPS, HR-TEM, EDS, XRD and N2 physisorption isotherm. The physical chemical properties of the materials were correlated with the catalytic results obtained in the asymmetric hydrogenation of 1-phenyl-1,2-propanedione. In 1-phenyl-1,2-propanedione hydrogenation the best results using chiral catalysts allowed 98% conversion and enantiomeric excess of 67% to (R)-1-hydroxy-1-phenyl-propan-2-one and 59% for (R)-2-hydroxy-1-phenylpropan-1-one. Catalyst recycling studies revealed that chiral nanoparticles immobilized on SiO2 are stable. These catalysts do not need extra amount of chiral modifier or inducer added in situ and could be reused without loss of enantioselectivity.
- Ruiz, Doris,M?ki-Arvela, P?ivi,Aho, Atte,Chiment?o, Ricardo,Claver, Carmen,Godard, Cyril,Fierro, José L.G.,Murzin, Dmitry Yu.
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- Structural and Mutagenesis Studies of the Thiamine-Dependent, Ketone-Accepting YerE from Pseudomonas protegens
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A wide range of thiamine diphosphate (ThDP)-dependent enzymes catalyze the benzoin-type carboligation of pyruvate with aldehydes. A few ThDP-dependent enzymes, such as YerE from Yersinia pseudotuberculosis (YpYerE), are known to accept ketones as acceptor substrates. Catalysis by YpYerE gives access to chiral tertiary alcohols, a group of products difficult to obtain in an enantioenriched form by other means. Hence, knowledge of the three-dimensional structure of the enzyme is crucial to identify structure–activity relationships. However, YpYerE has yet to be crystallized, despite several attempts. Herein, we show that a homologue of YpYerE, namely, PpYerE from Pseudomonas protegens (59 % amino acid identity), displays similar catalytic activity: benzaldehyde and its derivatives as well as ketones are converted into chiral 2-hydroxy ketones by using pyruvate as a donor. To enable comparison of aldehyde- and ketone-accepting enzymes and to guide site-directed mutagenesis studies, PpYerE was crystallized and its structure was determined to a resolution of 1.55 ?.
- Hampel, Sabrina,Steitz, Jan-Patrick,Baierl, Anna,Lehwald, Patrizia,Wiesli, Luzia,Richter, Michael,Fries, Alexander,Pohl, Martina,Schneider, Gunter,Dobritzsch, Doreen,Müller, Michael
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p. 2283 - 2292
(2018/10/20)
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- An improved enzymatic method for the preparation of (: R)-phenylacetyl carbinol
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(R)-Phenylacetyl carbinol (R-PAC) is one of the key chiral α-hydroxyketones utilized as a synthon in the synthesis of a number of pharmaceuticals having α- and β-adrenergic properties. An improved procedure for the preparation of the compound using the gl
- Li, Heng,Liu, Nan,Hui, Xian,Gao, Wen-Yun
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p. 32664 - 32668
(2017/07/07)
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- Assessing the stereoselectivity of: Serratia marcescens CECT 977 2,3-butanediol dehydrogenase
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α-Hydroxy ketones and vicinal diols constitute well-known building blocks in organic synthesis. Here we describe one enzyme that enables the enantioselective synthesis of both building blocks starting from diketones. The enzyme 2,3-butanediol dehydrogenase (BudC) from S. marcescens CECT 977 belongs to the NADH-dependent metal-independent short-chain dehydrogenases/reductases family (SDR) and catalyses the selective asymmetric reductions of prochiral α-diketones to the corresponding α-hydroxy ketones and diols. BudC is highly active towards structurally diverse diketones in combination with nicotinamide cofactor regeneration systems. Aliphatic diketones, cyclic diketones and alkyl phenyl diketones are well accepted, whereas their derivatives possessing two bulky groups are not converted. In the reverse reaction vicinal diols are preferred over other substrates with hydroxy/keto groups in non-vicinal positions.
- Médici, Rosario,Stammes, Hanna,Kwakernaak, Stender,Otten, Linda G.,Hanefeld, Ulf
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p. 1831 - 1837
(2017/07/15)
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- Organocatalytic Enantioselective Protonation for Photoreduction of Activated Ketones and Ketimines Induced by Visible Light
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The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation is reported. A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a non-covalent chiral organocatalyst is effective for these transformations. With the flexible use of a chiral Br?nsted acid or base in H+ transfer interchange to control the elusive enantioselective protonation, a variety of chiral α-hydroxy ketones and α-amino ketones were obtained with high yields and enantioselectivities.
- Lin, Lu,Bai, Xiangbin,Ye, Xinyi,Zhao, Xiaowei,Tan, Choon-Hong,Jiang, Zhiyong
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supporting information
p. 13842 - 13846
(2017/10/24)
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- Regio- and Stereoselective Aliphatic–Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis
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The catalytic asymmetric synthesis of chiral 2-hydroxy ketones by using different thiamine diphosphate dependent enzymes, namely benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), a variant of benzoylformate decarboxylase from?Pseudomonas putida (PpBFD-L461A), branched-chain 2-keto acid decarboxylase from Lactococcus lactis (LlKdcA) and a variant of pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G), was studied. Starting with the same set of substrates, substituted benzaldehydes in combination with different aliphatic aldehydes, PfBAL and PpBFD-L461A selectively deliver the (R)- and (S)-2-hydroxy-propiophenone derivatives, respectively. The (R)- and (S)-phenylacetylcarbinol (1-hydroxy-1-phenylacetone) derivatives are accessible in a similar way using LlKdcA and ApPDC-E469G, respectively. In many cases excellent stereochemical purities (>98 % enantiomeric excess) could be achieved. Hence, the regio- and stereochemistry of the product in the asymmetric aliphatic–aromatic cross-benzoin reaction can be controlled solely by choice of the appropriate enzyme or enzyme variant.
- Beigi, Maryam,Gauchenova, Ekaterina,Walter, Lydia,Waltzer, Simon,Bonina, Fabrizio,Stillger, Thomas,Rother, D?rte,Pohl, Martina,Müller, Michael
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supporting information
p. 13999 - 14005
(2016/09/21)
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- (S)-Selectivity in Phenylacetyl Carbinol Synthesis Using the Wild-Type Enzyme Acetoin:Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis
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Thiamine diphosphate (ThDP)-dependent enzymes are well known biocatalysts for the asymmetric synthesis of α-hydroxy ketones with preferential (R)-selectivity. Pharmaceutically relevant phenylacetyl carbinol (PAC) has been prepared with absolute (S)-configuration only on a few occasions using enzyme variants suitably designed through rational site-directed mutagenesis approaches. Herein, we describe the synthesis of (S)-phenylacetyl carbinol products with extended reaction scope employing the readily available wild-type ThDP-dependent enzyme acetoin:dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR) from Bacillus licheniformis. On a semipreparative scale, cross-benzoin-like condensations of methylacetoin (donor) and differently substituted benzaldehydes proceed with almost complete chemoselectivity yielding the target (S)-1-hydroxy-1-phenylpropan-2-one derivatives with high conversion efficiencies (up to 95%) and good enantioselectivities (up to 99%). Ao:DCPIP OR accepts hydroxy- and nitrobenzaldehydes and also sterically demanding substrates such as 1-naphthaldehyde and 4-(tert-butyl)benzaldehyde, which are typically poor acceptors in enzymatic transformations. The explorative synthesis of (S)-phenylpropionyl carbinol mediated by Ao:DCPIP OR via carboligation of benzaldehyde with 3,4-hexanedione is also reported. (Figure presented.).
- Giovannini, Pier Paolo,Lerin, Lindomar Alberto,Müller, Michael,Bernacchia, Giovanni,Bastiani, Morena De,Catani, Martina,Di Carmine, Graziano,Massi, Alessandro
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p. 2767 - 2776
(2016/09/13)
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- Biocatalytic route to chiral acyloins: P450-catalyzed regio- and enantioselective α-hydroxylation of ketones
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P450-BM3 and mutants of this monooxygenase generated by directed evolution are excellent catalysts for the oxidative α-hydroxylation of ketones with formation of chiral acyloins with high regioselectivity (up to 99%) and enantioselectivity (up to 99% ee). This constitutes a new route to a class of chiral compounds that are useful intermediates in the synthesis of many kinds of biologically active compounds.
- Agudo, Rubén,Roiban, Gheorghe-Doru,Lonsdale, Richard,Ilie, Adriana,Reetz, Manfred T.
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p. 950 - 956
(2015/01/30)
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- Catalytic scope of the thiamine-dependent multifunctional enzyme cyclohexane-1,2-dione hydrolase
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The thiamine diphosphate (ThDP)-dependent enzyme cyclohexane-1,2-dione hydrolase (CDH) was expressed in Escherichia coli and purified by affinity chromatography (Ni-NTA). Recombinant CDH showed the same Ci£C bond-cleavage and Ci£C bond-formation activitie
- Loschonsky, Sabrina,Waltzer, Simon,Fraas, Sonja,Wacker, Tobias,Andrade, Susana L. A.,Kroneck, Peter M. H.,Mueller, Michael
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p. 389 - 392
(2014/03/21)
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- Efficient 2-step biocatalytic strategies for the synthesis of all nor(pseudo)ephedrine isomers
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Chiral 1,2-amino alcohols are important building blocks for chemistry and pharmacy. Here, we developed two different biocatalytic 2-step cascades for the synthesis of all four nor(pseudo)ephedrine (N(P)E) stereoisomers. In the first one, the combination of an (R)-selective thiamine diphosphate (ThDP)-dependent carboligase with an (S)- or (R)-selective ω-transaminase resulted in the formation of (1R,2S)-NE or (1R,2R)-NPE in excellent optical purities (ee >99% and de >98%). For the synthesis of (1R,2R)-NPE, space-time yields up to ~26 g L-1 d-1 have been achieved. Since a highly (S)-selective carboligase is currently not available for this reaction, another strategy was followed to complement the nor(pseudo)ephedrine platform. Here, the combination of an (S)-selective transaminase with an (S)-selective alcohol dehydrogenase yielded (1S,2S)-NPE with an ee >98% and a de >99%. Although lyophilized whole cells are cheap to prepare and were shown to be appropriate for use as biocatalysts, higher optical purities were observed with purified enzymes. These synthetic enzyme cascade reactions render the N(P)E-products accessible from inexpensive, achiral starting materials in only two reaction steps and without the isolation of the reaction intermediates. This journal is the Partner Organisations 2014.
- Sehl, Torsten,Hailes, Helen C.,Ward, John M.,Menyes, Ulf,Pohl, Martina,Rother, Doerte
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supporting information
p. 3341 - 3348
(2014/06/10)
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- Extended reaction scope of thiamine diphosphate dependent cyclohexane-1,2-dione hydrolase: From C-C bond cleavage to C-C bond ligation
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ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) catalyzes the CC bond cleavage of cyclohexane-1,2-dione to 6-oxohexanoate, and the asymmetric benzoin condensation between benzaldehyde and pyruvate. One of the two reactivities of CDH was selectively knocked down by mutation experiments. CDH-H28A is much less able to catalyze the CC bond formation, while the ability for CC bond cleavage is still intact. The double variant CDH-H28A/N484A shows the opposite behavior and catalyzes the addition of pyruvate to cyclohexane-1,2-dione, resulting in the formation of a tertiary alcohol. Several acyloins of tertiary alcohols are formed with 54-94% enantiomeric excess. In addition to pyruvate, methyl pyruvate and butane-2,3-dione are alternative donor substrates for CC bond formation. Thus, the very rare aldehyde-ketone cross-benzoin reaction has been solved by design of an enzyme variant.
- Loschonsky, Sabrina,Wacker, Tobias,Waltzer, Simon,Giovannini, Pier Paolo,McLeish, Michael J.,Andrade, Susana L. A.,Müller, Michael
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supporting information
p. 14402 - 14406
(2015/02/19)
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- Two steps in one pot: Enzyme cascade for the synthesis of nor(pseudo)ephedrine from inexpensive starting materials
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Two steps in one pot: An enzyme cascade consisting of a lyase and an (R)- or (S)-selective ω-transaminase (TA) provides (1R,2R)-norpseudoephedrine and (1R,2S)-norephedrine in only two steps. The intermediate is not isolated in this one-pot reaction and the products are obtained in high enantio- and diastereomeric purity. Moreover, the by-product from the second reaction can be recycled to serve as the substrate for the first reaction. Copyright
- Sehl, Torsten,Hailes, Helen C.,Ward, John M.,Wardenga, Rainer,Von Lieres, Eric,Offermann, Heike,Westphal, Robert,Pohl, Martina,Rother, Doerte
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supporting information
p. 6772 - 6775
(2013/07/26)
-
- TCA cycle involved enzymes SucA and Kgd, as well as MenD: Efficient biocatalysts for asymmetric C-C bond formation
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Asymmetric mixed carboligation reactions of α-ketoglutarate with different aldehydes were explored with the thiamine diphosphate dependent enzymes SucA from E. coli, Kgd from Mycobacterium tuberculosis, and MenD from E. coli. All three enzymes proved to be efficient biocatalysts to selectively deliver chiral δ-hydroxy-γ-keto acids with moderate to excellent stereoselectivity. The high regioselectivity is due to the preserved role of α-ketoglutarate as acyl donor for these enzyme-catalyzed reactions.
- Beigi, Maryam,Waltzer, Simon,Fries, Alexander,Eggeling, Lothar,Sprenger, Georg A.,Müller, Michael
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supporting information
p. 452 - 455
(2013/04/10)
-
- Gold(III) complexes catalyze deoximations/transoximations at neutral pH
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Golden solution: A neutral solution of AuBr3, containing [AuBr2(OH)2]- in equilibrium with [AuBr 3(OH)]- and [AuBr4]-, promotes the chemoselective hydrolysis of robust oximes into carbonyl compounds without racemization (see scheme). The food additive diacetyl acts as a NH 2OH-trapping agent, thus avoiding the formation of gold nanoparticles and allows the reaction to run catalytically. Copyright
- Isart, Carles,Bastida, David,Bures, Jordi,Vilarrasa, Jaume
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experimental part
p. 3275 - 3279
(2011/05/12)
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- Enantioselective hydrogenation of ethyl pyruvate and 1-phenyl-1,2- propanedione on catalysts prepared by impregnation of colloidal platinum on SiO2
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The enantioselective hydrogenation of ethyl pyruvate and 1-phenyl-1,2-propanedione was studied at 298 K and 40 bar of H2 over colloidal Pt stabilized with cinchonidine (CD) and supported on silica. The catalysts were prepared by impregnation of colloidal
- Ruiz, Doris P.,Fierrob, Jose? L.G.,Reyes, Patricio A.
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experimental part
p. 262 - 269
(2010/09/03)
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- A combined NMR, DFT, and X-ray investigation of some cinchona alkaloid O-ethers
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(Chemical Equation Presented) Structures and conformational behavior of several cinchona alkaloid O-ethers in the solid state (X-ray), in solution (NMR and DFT), and in the gas phase (DFT) were investigated. In the crystal, O-phenylcinchonidine adopts the Open(3) conformation similar to cinchonidine, whereas the O-methyl ether derivatives of both cinchonidine and cinchonine are packed in the Closed(1) conformation. Dynamic equilibria in solutions of the alkaloids were revealed by combined experimental-theoretical spin simulation/iteration techniques for the first time. In the 1H NMR spectra in CDCl3 and toluene-d8 at room temperature, Closed(1) conformation was observed for the O-silyl ethers as a separate set of signals. For O-methyl ether derivatives Closed(1) could be separated only at -30°C in CDCl3 or toluene-d8 and for O-phenylcinchonidine at -70°C in CDCl3/CD2Cl2. The ratio between the Closed(2) and Open(3) conformers was estimated by analyzing the vicinal coupling constant 3JH9,H8 at ambient and low temperatures. The observed conformational equilibria of O-(tert-butyldimethylsilyl) cinchonidine in CDCl3 and toluene-d8 are in good agreement with the theoretically estimated equilibrium populations of the conformations according to Boltzmann statistics. The conformational equilibria of four cinchona alkaloid O-ether solutes in CDCl3 and toluene-d8 are discussed in the light of their relevance to the mechanism of 1-phenyl-1,2-propanedione (PPD) hydrogenation over cinchona alkaloid modified heterogeneous platinum catalysts. It was demonstrated that the conformation found to be abundant in the liquid phase has no direct correlation with the enantioselectivity of the PPD hydrogenation reaction.
- Busygin, Igor,Nieminen, Ville,Taskinen, Antti,Sinkkonen, Jari,Toukoniitty, Esa,Sillanpaeae, Reijo,Murzin, Dmitry Yu.,Leino, Reko
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p. 6559 - 6569
(2008/12/22)
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- Process for production of R-phenylacetylcarbinol by an enzymatic process in a two-phase system
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This application relates to a new process for the production of R-phenylacetylcarbinol by an enzymatic process in a liquid two-phase system.
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Page/Page column 4-5
(2008/06/13)
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- 4-Hydroxyacetophenone monooxygenase from Pseudomonas fluorescens ACB as an oxidative biocatalyst in the synthesis of optically active sulfoxides
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Recombinant 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB has been tested as a catalyst in sulfoxidation reactions on a set of aromatic sulfides. With a few exceptions, excellent enantioselectivities in the synthesis of chiral phenyl and benzyl sulfoxides were achieved. The bacterial Baeyer-Villiger monooxygenase was also shown to accept racemic sulfoxides, a prochiral diketone and an organoboron compound as substrates. This study demonstrates the great biocatalytic potential of this novel oxidative enzyme.
- De Gonzalo, Gonzalo,Torres Pazmino, Daniel E.,Ottolina, Gianluca,Fraaije, Marco W.,Carrea, Giacomo
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p. 130 - 135
(2007/10/03)
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- Synthesis of chiral catalyst modifiers by hydrosilylation of cinchonidine and their application in the hydrogenation of 1-phenylpropane-1,2-dione and ethyl pyruvate on a supported Pt/Al2O3 catalyst
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Four new chiral modifiers were synthesized in order to investigate the effect of distal modifier substitution in the hydrogenation of ethyl pyruvate and 1-phenylpropane-1,2-dione on a supported Pt/Al2O3 catalyst. The chiral modifiers
- Busygin, Igor,Toukoniitty, Esa,Sillanpaeae, Reijo,Murzin, Dmitry Yu.,Leino, Reko
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p. 2811 - 2821
(2007/10/03)
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- Oxidations catalyzed by phenylacetone monooxygenase from Thermobifida fusca
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Several organic sulfides, ketones and other organic systems have been tested as substrates in oxidation reactions catalyzed by the recently discovered phenylacetone monooxygenase from Thermobifida fusca. The biocatalytic properties of this Baeyer-Villiger monooxygenase have been studied, revealing reactivity with a large range of sulfides and ketones. Oxidations of several sulfoxides, an amine and an organoboron compound were also observed. The enzyme is able to oxidize a number of sulfides with excellent enantioselectivity, demonstrating the catalytic potential of this novel biocatalyst.
- De Gonzalo, Gonzalo,Torres Pazmino, Daniel E.,Ottolina, Gianluca,Fraaije, Marco W.,Carrea, Giacomo
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p. 3077 - 3083
(2007/10/03)
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- Asymmetric dihydroxylation of allenes
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We have used asymmetric dihydroxylation (AD) of allenes in order to synthesize chiral α-hydroxy ketones. This methodology has been applied to several aryl-substituted allenes. We have found that electron donating groups on the aromatic ring increase the efficiency of the reaction.
- Fleming, Steven A.,Carroll, Sean M.,Hirschi, Jennifer,Liu, Renmao,Pace, J. Lee,Redd, J. Ty
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p. 3341 - 3343
(2007/10/03)
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- Kinetics and modeling of 1-phenyl-1,2-propanedione hydrogenation
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Kinetics and modeling of 1-phenyl-1,2-propanedione hydrogenation over cinchonidine-modified Pt/Al2O3 catalyst is reported. Hydrogenation experiments carried out in a pressurized autoclave (288 K, 1.2-6.5 bar hydrogen) revealed interesting kinetic effects which inspired the model development. The enantioselectivity towards the (R)-configuration, as well as the reaction rate and regioselectivity, depended on the modifier concentration having a maximum. The enantio- and regioselective effects were explained by the kinetic model, which assumes different number of sites for adsorption of the carbonyl groups of the 1-phenyl-1,2-propanedione as well as for the cinchonidine adsorbed in flat and tilted modes. The number of adsorption sites needed for the different species were obtained from molecular considerations and the hydrogenation rate constants were determined along with the adsorption parameters by non-linear regression analysis. A comparison of model predictions with experimental data revealed that the model accounts for the kinetic regularities.
- Toukoniitty,Sevcikova,Maeki-Arvela,Waerna,Salmi,Murzin
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- Asymmetric nucleophilic addition reactions of aldehydes with optically active dithioacetals and their application to optically active α-hydroxy ketone synthesis
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Optically active dithioacetals were prepared by the reaction of acetals with dithiol (1) having a chiral binaphthyl skeleton. Asymmetric addition reactions of various aldehydes with lithiated dithioacetals smoothly proceeded to provide the corresponding c
- Taka, Hideo,Fujita, Ken-Ichi,Oishi, Akihiro,Taguchi, Yoichi
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p. 1487 - 1493
(2007/10/03)
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- Synthesis of optically active α-hydroxy carbonyl compounds by the catalytic, enantioselective oxidation if silyl enol ethers and ketene acetals with (salen)manganese(III) complexes
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A set of silyl enol ethers and ketene acetals 1a-h with α- and/or β-phenyl as well as alkyl substituents of different steric bulk has been submitted to the enantioselective catalytic oxidation by chiral (salen)Mn(III) complexes 3. Highest conversion and best enantioselectivities have been obtained with bleach rather than iodosobenzene as oxygen source for the active oxo-metal species. With regard to substrate structure ee values up to 89% have been achieved for enol ethers with short and unbranched alkyl substituents at the siloxy position. While β-phenyl groups are beneficial for enantiofacial control, phenyl substituents α to the siloxy functionality result in lower ee values, while the diphenyl-substituted derivative 1d displays the lowest stereoselectivity. The fact that β- versus α-phenyl substituents exhibit not only differences in the magnitude but also in the sense (opposite absolute product configuration) of the stereoselectivity may be utilized as a valuable mechanistic probe to assess steric and electronic effects in the substrate and the catalyst as a function of the type and pattern of substitution. Our results display that sterid interactions between the substrate and the oxo-metal complex are mainly responsible for the observed stereochemical preferences. Indeed, significantly increased enantioselectivities are achieved even for the remote siloxy group when bulkier derivatives are employed. In contrast, primarily electronic effects operate in the (salen)Mn(III) catalyst 3 since electron-donating groups in the 5,5' positions of the salicylaldelhyde ligand afford higher ee values in this catalytic oxidation. The skewed side-on approach (trajectory) of the substrate onto the oxo-metal catalyst is favored, the metallaoxetane mechanism adequately accounts for the observed enantioselectivities. Herewith a synthetically valuable method for the preparation of optically active α-hydroxy carbonyl products 2 has been made available through the catalytic, enantioselective oxidation of the silyl enol ethers 1 by (salen)Mn(III) complexes.
- Adam, Waldemar,Fell, Rainer T.,Stegmann, Veit R.,Saha-M?ller, Chantu R.
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p. 708 - 714
(2007/10/03)
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- Stereospecific formation of R-aromatic acyloins by Zymomonas mobilis pyruvate decarboxylase
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Recombinant pyruvate decarboxylase from Zymomonas mobilis catalysed the formation of R-aromatic acyloins of high optical purity from aromatic aldehydes and either pyruvate or acetaldehyde. The results are contrasted with those obtained with aliphatic acyloins and compared with those obtained with the pyruvate decarboxylase of Saccharomyces sp.
- Bornemann, Stephen,Crout, David H. G.,Dalton, Howard,Kren, Vladimir,Lobell, Mario,Dean, Gregory,Thomson, Nicholas,Turner, Margaret M.
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p. 425 - 430
(2007/10/03)
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- Kinetic resolution of racemic α-hydroxy ketones by lipase-catalyzed irreversible transesterification
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Asymmetric acetylation of racemic α-hydroxy ketones with isopropenyl acetate catalyzed by lipases afforded the optically active keto alcohols and acetates in high enantiomeric excess (up to 99%); an enzymatic kinetic resolution which may be performed on preparative scale.
- Adam, Waldemar,Diaz, Maria Teresa,Fell, Rainer T.,Saha-Moeller, Chantu R.
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p. 2207 - 2210
(2007/10/03)
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- Enantio- and regioselective reduction of α-diketones by baker's yeast
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Although yeast reduction of α-diketones 1 affords a mixture of two α-hydroxy ketones and a vic-diol, the use of methyl vinyl ketone as an enzyme inhibitor prevents the production of the diol. Regioselectivity in the reduction to afford α-hydroxy ketones i
- Nakamura, Kaoru,Kondo, Shin-Ichi,Kawai, Yasushi,Hida, Kouichi,Kitano, Kazutada,Ohno, Atsuyoshi
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p. 409 - 412
(2007/10/03)
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- Improved Conditions for the production and Chatacterization of 1-Arylpropane-1,2-diols and Related Compounds
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Improved conditions for the production and characterization of 1-arylpropane-1,2-diols and related compounds were developed.Experimental conditions providing highly enhanced activity of pyruvate decarboxylase in bakers' yeast in the presence of pyruvate, thiamine pyrophosphate, and magnesium(II) salt were applied to the preparation of (R)-1-hydroxy-1-phenyl-2-propanone from benzaldehyde.Subsequent reduction with bakers' yeast efficiently afforded 1-phenyl-1,2-propanediol (35percent).The composition of its stereoisomers was precisely determined, and the major (1R,2S)-isomer (89percent of the total mixture) could be isolated by recrystallizing the corresponding benzoate.The analytical method for identifying the stereoisomeric composition was also effective for the determination of 5-phenyl-4-pentene-2,3-diol, the biotransformation product from cinnamaldehyde, the vinylogous substrate of benzaldehyde.Furthermore, the structural characterization of 1(2-furyl)propane-1,2-diol, which was obtained from furfural (28percent) by the action of brewers' yeast Saccharomyces cerevisiae (carlsbergensis), is described.The major (1S,2S)-isomer could be isolated by recrystallizing the crude product.
- Mochizuki, Naoki,Hiramatsu, Shigeki,Sugai, Takeshi,Ohta, Hiromichi,Morita, Hiroshi,Itokawa, Hideji
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p. 2282 - 2291
(2007/10/03)
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- Method of preparing optically active alcohols which consist substantially or entirely of one enantiomer
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The invention relates to a method of preparing optically active alcohols which consist substantially (at least 75% e.e.) or entirely of one enantiomer of formula 4 STR1 wherein R and A are as defined therein. The method comprises, which maintaining enantiomeric excess, converting an optically active cyanohydrin of formula 1 STR2 into optically active protected cyanohydrin of formula 2 STR3 converting the protected cyanohydrin of formula 2 into an optically active compound of formula 3 STR4 removing the protecting group B.
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