- Protonic Reorganization and Substrate Structure in Catalysis by Serine Proteases
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Proton inventories (rate measurements in binary mixtures of protium and deuterium oxides) have been used to estimate the number of protons involved in hydrolytic catalysis by serine proteases with various substrates.Trypsin with the oligopeptide analogue
- Elrog, James P.,Hogg, John L.,Quinn, Daniel M.,Venkatasubban, K. S.,Schowen, Richard L.
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- N-heterocyclic carbene catalyzed enantioselective [3 + 2] dearomatizing annulation of saturated carboxylic esters with n-iminoisoquinolinium ylides
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The dearomatizing annulation reaction is a significant challenge in organic chemistry. The direct activation of α-carbons of simple saturated esters, as nucleophiles, is an important synthesis strategy. In the present study, we disclose [3 + 2] dearomatizing annulation reactions with direct activating α-carbons of saturated carboxylic esters and N-iminoisoquinolinium ylides, which possess highly enantioselective characteristics, catalyzed by N-heterocyclic carbenes (NHCs). The protocol achieves isoquinoline dearomatization and the construction of tricyclic chiral products under mild conditions with good yield, substrate tolerance, and diastereoselectivity as well as excellent enantioselectivity.
- Zhang, Pengfei,Zhou, Yu,Han, Xu,Xu, Jinyi,Liu, Hong
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- Isothiourea-catalysed transfer hydrogenation of α,β-unsaturated para-nitrophenyl esters
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A protocol for the isothiourea-catalysed transfer hydrogenation of α,β-unsaturated para-nitrophenyl esters using Hantzsch ester has been developed. Good to excellent yields are observed using α,β-unsaturated aryl esters bearing electron-withdrawing β-subs
- Smith, Andrew D.,Wu, Jiufeng,Young, Claire M.
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- Self-supported N-heterocyclic carbenes and their use as organocatalysts
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The study of N-heterocyclic carbenes (NHCs) as organocatalysts has proliferated in recent years, and they have been found to be useful in a variety of reactions. In an attempt to further expand their utility and to study their recyclability, we designed and synthesized a series of self-supported NHCs in which the catalytic carbene groups form part of a densely functionalized polymer backbone, and studied them as organocatalysts. Of the self-Supported NHCs examined, a benzimidazole derived polymer with flexible linkers connecting the catalytic groups was found to be the most efficient organocatalyst in a model benzoin condensation reaction, and thus it was used in a variety of such reactions, including some involving catalyst recycling. Furthermore, it was also used to catalyze a set of redox esterification reactions involving conjugated unsaturated aldehydes. In all of these reactions the catalyst afforded good yield of the desired product and its polymeric nature facilitated product purification.
- Ma, Shuang,Toy, Patrick H.
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- Olefins from biomass feedstocks: Catalytic ester decarbonylation and tandem Heck-type coupling
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With the goal of avoiding the need for anhydride additives, the catalytic decarbonylation of p-nitrophenylesters of aliphatic carboxylic acids to their corresponding olefins, including commodity monomers like styrene and acrylates, has been developed. The reaction is catalyzed by palladium complexes in the absence of added ligands and is promoted by alkali/alkaline-earth metal halides. Combination of catalytic decarbonylation and Heck-type coupling with aryl esters in a single pot process demonstrates the viability of employing a carboxylic acid as a "masked olefin" in synthetic processes. This journal is
- John, Alex,Hogan, Levi T.,Hillmyer, Marc A.,Tolman, William B.
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supporting information
p. 2731 - 2733
(2015/03/05)
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- Organocatalytic activation of alkylacetic esters as enolate precursors to react with α,β-unsaturated imines
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Asymmetric functionalization of alkylacetic esters and their derivatives is traditionally achieved via preformed enolates with chiral auxiliaries. Catalytic versions of such transformations are attractive but challenging. A direct catalytic activation of simple alkylacetic esters via N-heterocyclic carbene organocatalysts to generate chiral enolate intermediates for highly enantioselective reactions is reported.
- Hao, Lin,Chen, Shaojin,Xu, Jianfeng,Tiwari, Bhoopendra,Fu, Zhenqian,Li, Tong,Lim, Jieyan,Chi, Yonggui Robin
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supporting information
p. 4956 - 4959
(2013/10/22)
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- Fingerprint lipolytic enzymes with chromogenic p-nitrophenyl esters of structurally diverse carboxylic acids
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A series of structurally diverse chromogenic esters, including a new compound (4-nitrophenyl 2-methylpentanoate), has been synthesized, constituting an array of 17 substrates which could be applied to rapidly fingerprint the activity of lipases or esterases to reveal their substrates specificity and functional characteristics. Combined with genetic technology such as "data mining" and directed evolution, such fingerprints might be a promising platform for discovery of potentially useful enzymes in industrial application. The fingerprint of commercially available Lipase-B from Candida antarctica as a model enzyme was first measured to confirm the reliability of this method. Then three new enzymes mined from genomic libraries were successfully fingerprinted, revealing the functional characteristics of those enzymes. Among them, the enzyme SrfAD was founded with specific substrate preference towards cycloalkyl carboxylic esters and aromatic esters, making it more promising in synthetic utilities than other tested enzymes.
- Qian, Le,Liu, Jia-Yan,Liu, Jia-Ying,Yu, Hui-Lei,Li, Chun-Xiu,Xu, Jian-He
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experimental part
p. 22 - 26
(2012/02/06)
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- An invesigation of activities and paraoxon sensitivities of hepatic aliesterases in β-naphthoflavone-treated rats
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Aliesterases (carboxylesterases, EC 3.1.1.1) are serine esterases which may protect acetylcholinesterase during organophosphorus insecticide intoxication by providing alternative phosphorylation sites. Levels of hepatic aliesterase activity were investigated after the intraperitoneal administration of β-naphthoflavone (BNF) to female rats using nine 4-nitrophenyl esters as substrates (including straight and branched chain aliphatic and aromatic esters) and 1-naphthyl acetate. In addition, the in vitro sensitivities of aliesterases to inhibition by paraoxon, the active metabolite of the common insecticide parathion, were studied. Hepatic aliesterases from BNF-treated rats displayed lower activities than those from controls with all substrates except 4-nitrophenyl phenylbutyrate and isovalerate. The aliesterases from BNF-treated rats were more sensitive to paraoxon inhibition with 4-nitrophenyl phenylbutyrate, valerate, and butyrate. Esterases hydrolyzing 4-nitrophenyl butyrate, valerate, and branched chain esters were most sensitive to paraoxon inhibition while those hydrolyzing 4-nitrophenyl hexanoate and aromatic esters were least sensitive. The results suggested that BNF-induced changes in hepatic aliesterases could alter responses to organophosphates. Keywords: Aliesterases; β-Naphthoflavone; Paraoxon; Organophosphate
- Watson, Angela M.,Chambers, Howard,Chambers, Janice E.
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p. 217 - 226
(2007/10/03)
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- A New and Efficient Esterification Reaction via Mixed Anhydrides by the Promotion of a Catalytic Amount of Lewis Acid
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In the presence of a catalytic amount of Lewis acid, various carboxylic esters or S-phenyl carbothioates are prepared in excellent yields by the respective reactions of equimolar amounts of silyl carboxylates and alkyl silyl ethers or phenyl silyl sulfides with 4-trifluoromethylbenzoic anhydride.
- Miyashita, Mitsutomo,Shiina, Isamu,Miyoshi, So,Mukaiyama, Teruaki
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p. 1516 - 1527
(2007/10/02)
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- Nitrogen Participation in the Deacylation of D-Glucosamine and α-Chymotrypsin Derivatives. Explanation of the Stereospecificity of Acyl-α-Chymotrypsin Hydrolysis
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The hydrolysis of ethyl 3,4,6-tri-O-acetyl-2-deoxy-2-amino-β-D-glucopyranoside and acylated α-chymotrypsins has been investigated.Both transformations are catalyzed by neighbouring nitrogen atom participation.The stereospecificity of acylated enzyme hydrolysis can be explained by the specific steric hindrance of nitrogen participation.Keywords: selective deacylation, stereospezific ester hydrolysis, acylated derivatives of α-chymotrypsin, 2-amino-2-deoxy-glucose
- Oetvoes, Laszlo,Kraicsovits, Ferenc
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p. 5009 - 5014
(2007/10/02)
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- A New and Efficient Method for the Preparation of S-Phenyl Carbothioates via Mixed Anhydrides Using Active Titanium(IV) Salts
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In the presence of a catalytic amount of titanium(IV) salt, various S-phenyl carbothioates are prepared in excallent yields by the reaction of nearly equimolar amounts of silyl derivatives of carboxylic acids and benzenethiols with p-trifluoromethylbenzoic anhydride.
- Mukaiyama, Teruaki,Miyashita, Mitsutomo,Shiina,, Isamu
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p. 1747 - 1750
(2007/10/02)
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- β-substituted β-phenylpropionyl chymotrypsins. Structural and stereochemical features in stable acyl enzymes
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In order to develop effective alternate substrate inhibitors for serine proteases, we have prepared a series of β-substituted β-phenylpropionic acid esters related to some systems known to form stable acyl enzymes with α-chymotrypsin. Some of these compounds were prepared in enantiomerically pure form by asymmetric synthesis. Acyl enzyme species were generated from chymotrypsin by reaction with the active esters, and the progress of deacylation was monitored by the proflavin displacement assay. In some cases, it was possible to distinguish two different deacylation rates that correspond to the two enantiomers. β-Phenylpropionic acyl enzymes with β-substituents that are nonpolar were not especially stable, but a number of the polar derivatives and particularly the acylamino derivatives showed slow rates of deacylation (k(d) less than 0.005 min-1), with three systems showing deacylation enantioselectivities in the range of 500-1500. These results are consistent with a model in which additional stabilization of the acyl enzyme and enantioselectivity in the deacylation process derives from an additional hydrogen bond between the acyl enzyme species (as an acceptor) and the enzyme (as a donor). A number of active site residues that might be involved in this hydrogen bond are discussed.
- Reed,Katzenellenbogen
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p. 1162 - 1176
(2007/10/02)
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- A water soluble dimeric steroid with catalytic properties. Rate enhancements from hydrophobic binding
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Dimeric steroids can be formed by reductive amination of terephthalaldehyde with 3-amino steroids using cyanoborohydride.An amino group in the 11 β-position can be blocked using a formyl group, and this can be removed by acid hydrolysis after dimerization.Trifluoroacetyl is not a suitable blocking group; although it can be removed by acid hydrolysis from monomeric steroids, it was only removed from the dimer under forcing conditions which caused degradation.The dimeric steroid is a catalyst for the hydrolysis of arylpropionate esters with good leaving groups.Acylation is markedly accelerated by hydrophobic binding of the aryl group of the substrate to the steroids.Rate enhancements, relative to imidazole, of up to 5.5 x 102 were obtained, and analysis of the data shows that the potential rate enhancement is 1.1 x 105.The magnitude of the hydrophobic binding is consistent with what was seen with earlier catalysts.Aggregation, even at very low concentrations, was a problem with anionic substrates.
- Guthrie, J. Peter,Cossar, John,Dawson, Brian A.
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p. 2456 - 2469
(2007/10/02)
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- Carboxamidomethyl esters as reactive substrates for alpha-chymotrypsin. Orientational effects of hydrogen-bonding interactions.
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Effects of hydrogen-bonding interactions of amide groups on reactivity of esters to alpha-chymotrypsin were studied. Of the methyl esters studied, only that from acetyl-L-phenylalanine has k3 rate-limiting. In methyl beta-phenylpropionates an alpha-acetamido substituent increased k2 greater than 550 times, k3 approximately 5 times; an alpha-acetylclycyloxy substituent increased k2 approximately 2 times, k3 approximately 6 times, both in comparison with the alpha-acetoxy esters. Essentially all carboxamidomethyl esters studied have k3 rate-limiting; reactivity to hydroxide is only 4 times that of methyl esters. In alpha-substituted beta-phenylpropionates, carboxamido-methyl esters show k2 values greater than 110 times greater than 280 times, greater than 26 times, and 7 times the k2 values of the methyl esters for the alpha substituents, acetoxy, acetylglycyloxy, hydroxy, and hydrogen, respectively. In esters of alpha-acetamido acids, carboxamidomethyl esters show k2 values 44 times, greater than 110 times, greater than 12 times, and approximately 33 times the k2 values of the methyl esters of glycine, alanine, leucine, and phenylalanine, respectively. Cyanomethyl esters also had k3 rate-limiting. Hydrogen-bonding to the enzyme of either an alpha-acetamido group or a carboxamidomethyl group combined with bonding of the beta-aryl group, orients the hydrolyzing groups properly, increasing k2. Hydrogen-bonding of both alpha-acetamido and carboxamido-methyl groups is effective to a lesser degree. The amide group appears to have small effects on Ks as hydrogen bonding is balanced by desolvation. It is proposed that desolvation during bonding increases k2 and Ks.
- Cohen,Torem,Vaidya,Ehret
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p. 4722 - 4728,4723, 4725
(2007/10/12)
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