- LipG9-mediated enzymatic kinetic resolution of racemates: Expanding the substrate-scope for a metagenomic lipase
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Enzymes are the main biocatalysts of biological systems and nowadays they play an important role in asymmetric organic synthesis. Microorganisms are the main source for enzymes, however, just a very small portion of them are culturable at lab conditions and, as an alternative, metagenomics approaches allow new enzymes to be accessed from so-called “non-culturable” microorganisms. Several classes of metagenomic enzymes have been described in literature. Nevertheless, studies about their potential for asymmetric biotransformation are underexploited. Therefore, we present our recent efforts to establish the substrate-scope of LipG9, a metagenomic lipase, in enzymatic kinetic resolution (EKR) of chiral substances. LipG9 was previously isolated, immobilized and successfully applied in EKR of aliphatic alcohols. In this study, a series of resolvable chiral substances were assayed with LipG9, and secondary benzyl alcohols/esters were preferentially resolved in a much superior enantioselectivity (E > 200) than those described for aliphatic alcohols (E from 4 to 63). In an opposite way, Im-LipG9 did not present activity for tertiary alcohols, amines and lactones. When compared to commercial lipases, Im-LipG9 enantioselectivity was superior to Candida rugosa lipase and equivalent to Candida antarctica lipase B. Thus, the chemo and enantioselectivity of LipG9 in EKR reactions were identified and its potential for asymmetric synthetic approaches was demonstrated.
- Thomas, Juliana Christina,Alnoch, Robson Carlos,Costa, Allen Carolina dos Santos,Bandeira, Pamela Taisline,Burich, Martha Daniela,Campos, Suelem Kluconski,de Oliveira, Alfredo Ricardo Marques,de Souza, Emanuel Maltempi,Pedrosa, Fabio de Oliveira,Krieger, Nadia,Piovan, Leandro
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- Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers
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When benzylic and allylic alcohols were treated with enol acetate in the presence of a catalytic amount of a rhenium complex, ReBr(CO)5, the carbon-carbon bond formation of the alcohols and enol acetate smoothly proceeded to give the corresponding ketones and aldehyde in moderate to good yields. For the reaction of allylic alcohols, γ,δ-unsaturated carbonyl compounds were obtained in good yields. When ethers were used instead of alcohols as the alkylated agent, two alkyl moieties on the ethers were utilized on the reaction.
- Umeda, Rui,Takahashi, Yuuki,Yamamoto, Takaaki,Iseki, Hideki,Osaka, Issey,Nishiyama, Yutaka
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supporting information
p. 92 - 101
(2018/11/01)
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- Rhenium complex-catalyzed coupling reaction of enol acetates with alcohols
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The reaction of enol acetates with alcohols in the presence of a catalytic amount of a rhenium complex, such as ReBr(CO)5, produced the corresponding ketones and aldehydes in moderate to good yields. It was suggested that the preparation of an ether, an intermolecular dehydrated product, was the first step of the reaction.
- Umeda, Rui,Takahashi, Yuuki,Nishiyama, Yutaka
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p. 6113 - 6116
(2015/01/09)
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- Separation of enantiopure m-substituted 1-phenylethanols in high space-time yield using Bacillus subtilis esterase
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A recombinant Bacillus subtilis esterase (BsE) expressed in E. coli was found to exhibit excellent enantioselectivity (E was always greater than 100) towards m-substituted 1-phenylethanol acetates in the enantioselective hydrolysis reaction. An explanation for the high enantioselectivity observed towards these substrates was provided by molecular modeling. Moreover, the BsE also showed strong tolerance towards a high concentration of m-substituted 1-phenylethanol acetates (up to 1 M). Based on these excellent catalytic properties of BsE, a kind of m-substituted 1-phenylethanols, (R)-1-(3-chlorophenyl)ethanol, was efficiently synthesized in space-time yield of 920 g per L per day and 97% ee, indicating that the BsE was considered as a potentially ideal and promising biocatalyst for large-scale production of optically active m-substituted 1-phenylethanols. The Royal Society of Chemistry 2013.
- Zheng, Gao-Wei,Liu, Xu-Yun,Zhang, Zhi-Jun,Tian, Ping,Lin, Guo-Qiang,Xu, Jian-He
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p. 20446 - 20449
(2013/11/06)
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- Modular P-OP ligands in rhodium-mediated asymmetric hydrogenation: A comparative catalysis study
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Highly efficient and enantioselective hydrogenation reactions for α-(acylamino)acrylates, itaconic acid derivatives and analogues, α-substituted enol ester derivatives, and α-arylenamides (25 substrates) catalyzed by chiral cationic rhodium complexes of a set of P-OP ligands have been developed. The catalytic systems derived from these P-OP ligands provided a straightforward access to enantiomerically enriched α-amino acid, carboxylic acid, amine, and alcohol derivatives that are valuable chiral building blocks. Excellent efficiencies (full conversion in all cases) and extremely high enantiomeric excesses (94-99% ee) were achieved for a wide range of α-substituted enol ester derivatives, regardless of the substitution pattern. The R-oxy group of the ligand (methoxy or triphenylmethoxy) strongly influences the enantioselectivity and catalytic activity. Greater steric bulk around the metal centre correlated to greater (or similar) enantioselectivity, but also to slower hydrogenation. Furthermore, the hydrogenation rates observed with the four model substrates follow the same trend, independently of the R-oxy group of the ligand: methyl 2-acetamidoacrylate>dimethyl itaconate>1-phenylvinyl acetate>N-(1- phenylvinyl)acetamide. A substrate-to-catalyst ratio (S/C) of up to 10,000:1 was sufficient for total hydrogenation of a model substrate of intermediate reactivity (dimethyl itaconate), and did not imply any loss in conversion or enantioselectivity. Copyright
- Nunez-Rico, Jose L.,Etayo, Pablo,Fernandez-Perez, Hector,Vidal-Ferran, Anton
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p. 3025 - 3035
(2013/01/15)
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- Dynamic kinetic resolution of a wide range of secondary alcohols: Cooperation of dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium and CAL-B
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The substrate scope in the dynamic kinetic resolution ofsecondary alcohols was studied by using 31 structurallydifferent alcohols and isopropenyl acetate in the presence ofdicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (Novozym 435, CAL-B) in toluene. The enzyme and the ruthenium complex were shown to function in a highly compatible manner allowing the conversion of the racemic alcohols into the (R)-acetates in practically theoretical yields and, in most cases, ee values exceeding 99%. The results are fully comparable to those published previously by using earlier reported, state-of-the-art ruthenium-based catalysts for the alcohol racemization. A clear benefit of the dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium system, when compared to other (cyclopentadienyl)ruthenium racemization catalysts, is its simple and cost-efficient preparation. The substrate scope of 31 secondary alcohols was studied in the dynamic kinetic resolution by utilizing dicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (CAL-B) in the acylation with isopropenyl acetate in toluene at room temperature. The secondary alcohols were transformed into highly enantiopure (R)-acetates (in most cases ee > 99%) in close to quantitative isolatedyields. Copyright
- Paeivioe, Mari,Mavrynsky, Denys,Leino, Reko,Kanerva, Liisa T.
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supporting information; experimental part
p. 1452 - 1457
(2011/04/22)
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- Evaluation of snake venom phospholipase A2: Hydrolysis of non-natural esters
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Phospholipase A2 from the rattlesnake Crotalus durissus terrificus was employed for the first time to test its enantioseletivity on the hydrolysis of different non-natural esters. It was observed that the structure of this small enzyme is restrictive in the choice of its lipase action with non-natural substrates. Two forms of the enzyme were used; free and as its cross-linked enzyme aggregate (CLEA). With all substrates, the free enzyme showed activity similar to the CLEA preparation. The advantage of the CLEA phospholipase is the possibility to reuse it in several consecutive reactions without a decrease of activity and selectivity with good but higher yields and ee than with the free enzyme.
- Pirolla, Renan A. S.,Baldasso, Paulo A.,Marangoni, Se?rgio,Moran, Paulo J. S.,Rodrigues, Jose? Augusto R.
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experimental part
p. 300 - 307
(2011/10/05)
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- A tandem and fully enzymatic procedure for the green resolution of chiral alcohols: Acylation and deacylation in non-aqueous media
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A green and fully enzymatic procedure for the resolution of chiral alcohols through lipase/esterase-catalyzed acylation and subsequent lipase-catalyzed aminolysis using anhydrous ammonia was demonstrated. Both enantiomers can be obtained in high ee values (up to >99%) under ambient reaction conditions. The solvent and acyl donors can be recycled, and the enzyme can be reused for up to five times.
- Wang, Bo,Jiang, Ling,Wang, Jue,Ma, Jingbo,Liu, Min,Yu, Hongwei
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p. 980 - 985
(2011/10/04)
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- Chiral rhodium complexes derived from electron-rich phosphine-phosphites as asymmetric hydrogenation catalysts
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Two new chiral cationic rhodium(I) complexes derived from electron-rich dicyclohexylphosphine-phosphite ligands were prepared from enantiopure Sharpless epoxy ethers. The best-performing catalyst system, which bears a less bulky methyl ether moiety, exhibited remarkably high enantioselectivity (up to 99% ee) and reactivity (up to >2500 TON) in asymmetric hydrogenation reactions of various functionalized alkenes (α-(acylamino)acrylates, itaconic acid derivatives, α-substituted enol esters and α-arylenamides). Our synthetic methodology has been successfully applied to the enantioselective synthesis of the antiepileptic drug (R)-lacosamide (Vimpat).
- Etayo, Pablo,Nunez-Rico, Jose L.,Vidal-Ferran, Anton
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experimental part
p. 6718 - 6725
(2012/02/05)
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- Benzylic-acetoxylation of alkylbenzenes with PhI(OAc)2 in the presence of catalytic amounts of TsNH2 and I2
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Treatment of alkylbenzenes with (diacetoxyiodo)benzene in the presence of catalytic amounts of p-toluenesulfonamide or p-nitrobenzenesulfonamide, and molecular iodine in 1,2-dichloroethane at 60 °C gave the corresponding (α-acetoxy)alkylbenzenes in good to moderate yields. The present reaction is a simple method for the introduction of an acetoxy group to the benzylic position of alkylbenzenes.
- Baba, Haruka,Moriyama, Katsuhiko,Togo, Hideo
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experimental part
p. 4303 - 4307
(2011/08/22)
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- Silver triflate catalyzed acetylation of alcohols, thiols, phenols, and amines
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A variety of alcohols, thiols, phenols, and amines were subjected to acetylation reaction using acetic anhydride in the presence of catalytic quantity of silver triflate. The method described has a wide range of applications, proceeds under mild conditions, does not involve cumbersome workup, and the resulting products are obtained in high yields within a reasonable time. Georg Thieme Verlag Stuttgart · New York.
- Das, Rima,Chakraborty, Debashis
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experimental part
p. 1621 - 1625
(2011/06/25)
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- Escherichia coli BioH: A highly enantioselective and organic solvent tolerant esterase for kinetic resolution of sec-alcohols
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Escherichia coli BioH, which is obligatory for biotin synthesis, was found to be an organic solvent tolerant esterase with high enantioselectivity for the kinetic resolution of sec-alcohols using free enzyme powder. With this esterase, a variety of racemic sec-alcohols were efficiently resolved with ee values of up to 99%.
- Wang, Bo,Tang, Xiaoling,Liu, Ji,Yu, Hongwei
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supporting information; experimental part
p. 6360 - 6364
(2011/01/04)
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- Enzymatic kinetic resolution of (RS)-1-(phenyl)ethanols by Burkholderia cepacia lipase immobilized on magnetic nanoparticles
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Lipase from Burkholderia cepacia immobilized on superparamagnetic nanoparticles using adsorption and chemisorption methodologies was efficiently applied as recyclable biocatalyst in the enzymatic kinetic resolution of (RS)-1-(phenyl)ethanols via transesterification reactions. (R)-Esters and the remaining (S)-alcohols were obtained with excellent enantiomeric excess (> 99percent), which corresponds to a perfect process of enzymatic kinetic resolution (conversion 50percent, E > 200). The transesterification reactions catalysed with B. cepacia lipase immobilized by the glutaraldehyde method showed the best results in terms of reusability, preserving the enzyme activity (conversion 50percent, E > 200) for at least 8 successive cycles.
- Rebelo, Lya P.,Netto, Caterina G. C. M.,Toma, Henrique E.,Andrade, Leandro H.
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experimental part
p. 1537 - 1542
(2010/11/16)
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- Enantioselective transesterification catalysis by Candida antarctica lipase immobilized on superparamagnetic nanoparticles
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Lipase B from Candida antarctica can be directly immobilized onto functionalized superparamagnetic nanoparticles, preserving its enzymatic activity in the enantioselective transesterification of secondary alcohols, with excellent results in terms of enantiomeric discrimination. The immobilized enzyme can be easily recovered with a magnet, allowing its reuse with negligible loss of activity.
- Netto, Caterina G.C.M.,Andrade, Leandro H.,Toma, Henrique E.
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experimental part
p. 2299 - 2304
(2010/03/04)
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- Baeyer-Villiger monooxygenase-catalyzed kinetic resolution of racemic α-alkyl benzyl ketones: enzymatic synthesis of α-alkyl benzylketones and α-alkyl benzylesters
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The application of three BVMOs for the enantioselective oxidation of 3-phenylbutan-2-ones with different substituents in the aromatic moiety is described. By choosing the appropriate biocatalyst and substrate combination, chiral ketones and esters can be obtained with excellent enantiopurities. This methodology could also be applied to the resolution of racemic α-alkyl benzylketones with longer alkyl chains as well as with two substituted α-substituted benzylacetones. A kinetic analysis revealed that the BVMOs studied effectively convert all tested compounds showing that the enzymes are tolerant towards the substrate structure while being highly enantioselective. These properties render BVMOs as valuable biocatalysts for the preparation of compounds with high interest in organic synthesis.
- Rodriguez, Cristina,Gonzalo, Gonzalo de,Torres Pazmino, Daniel E.,Fraaije, Marco W.,Gotor, Vicente
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experimental part
p. 1168 - 1173
(2009/10/02)
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- Immobilized Manihot esculenta preparation as a novel biocatalyst in the enantioselective acetylation of racemic alcohols
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The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfully immobilized on calcium alginate hydrogels. This preparation has been tested as a chiral biocatalyst in the enzymatic acylation of a set of racemic aromatic alcohols. Depending on the reaction conditions, excellent enantioselectivities can be achieved. Some parameters that can alter the biocatalytic properties of the enzyme, such as solvent, temperature, acyl donor and substrate structure have been studied exhaustively in order to establish a deeper knowledge of this novel biocatalyst.
- Machado, Luciana L.,Lemos, Telma L.G.,de Mattos, Marcos Carlos,de Oliveira, Maria da Conceicao F.,de Gonzalo, Gonzalo,Gotor-Fernandez, Vicente,Gotor, Vicente
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p. 1418 - 1423
(2008/12/20)
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- A C2-symmetric metallocene-pyrrolidinopyridine nucleophilic catalyst for asymmetric synthesis
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A C2-symmetric nucleophilic catalyst, (R,R)-3,5-diferrocenyl-4- (2′,5′-dimethylpyrrolidino)pyridine, was synthesised in three steps from commercially available (S,S)-hexane-2,5-diol. Application to the kinetic resolution of secondary alcohols (0.5 mol% loading) resulted in selectivity factors (s) of up to 6. Georg Thieme Verlag Stuttgart.
- Nguyen, Huy V.,Motevalli, Majid,Richards, Christopher J.
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p. 725 - 728
(2008/01/01)
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- Synthesis of o-nitrosoacylbenzenes from o-nitrobenzyl alcohols and their derivatives
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Nitration of substituted benzyl alcohols, as well as ethers and esters derived therefrom, with nitric acid in acetic anhydride was studied. The corresponding o-nitrobenzyl alcohols and their derivatives formed as the primary products are capable of being converted into o-nitrosoacylbenzenes by the action of acids. Pleiades Publishing, Inc., 2006.
- Gazzaeva,Fedotov,Trofimova,Popova,Mochalov,Zefirov
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- Asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens
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A new asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens has been found. Although alcohols are not the natural substrates for this enzyme, a high R enantioselectivity was observed. Stereochemical studies showed that variations in substrate structure lead to strong variations in enantioselectivity. The highest enantioselectivities are obtained when the β-carbon of the secondary alcohol is tertiary or quaternary.
- Hatzakis, Nikos S.,Smonou, Ioulia
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p. 325 - 337
(2007/10/03)
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- Combined ruthenium(II) and lipase catalysis for efficient dynamic kinetic resolution of secondary alcohols. Insight into the racemization mechanism
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Pentaphenylcyclopentadienyl ruthenium complexes (3) are excellent catalysts for the racemization of secondary alcohols at ambient temperature. The combination of this process with enzymatic resolution of the alcohols results in a highly efficient synthesis of enantiomerically pure acetates at room temperature with short reaction times for most substrates. This new reaction was applied to a wide range of functionalized alcohols including heteroaromatic alcohols, and for many of the latter, enantiopure acetates were efficiently prepared for the first time via dynamic kinetic resolution (DKR). Different substituted cyclopentadienyl ruthenium complexes were prepared and studied as catalysts for racemization of alcohols. Pentaaryl-substituted cyclopentadienyl complexes were found to be highly efficient catalysts for the racemization. Substitution of one of the aryl groups by an alkyl group considerably slows down the racemization process. A study of the racemization of (S)-1-phenylethanol catalyzed by ruthenium hydride η5-Ph5CpRu(CO) 2H (8) indicates that the racemization takes place within the coordination sphere of the ruthenium catalyst. This conclusion was supported by the lack of ketone exchange in the racemization of (S)-1-phenylethanol performed in the presence of p-tolyl methyl ketone (1 equiv), which gave 1% of 1-(p-tolyl)ethanol. The structures of ruthenium chloride and iodide complexes 3a and 3c and of ruthenium hydride complex 8 were confirmed by X-ray analysis.
- Martin-Matute, Belen,Edin, Michaela,Bogar, Krisztian,Kaynak, F. Betuel,Baeckvall, Jan-E.
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p. 8817 - 8825
(2007/10/03)
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- Enantioselective Rh-catalyzed hydrogenation of enol acetates and enol carbamates with monodentate phosphoramidites
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(Chemical Equation Presented) Monodentate phosphoramidites, in particular PipPhos and its octahydro analogue, are excellent ligands for the rhodium-catalyzed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates up to 98% ee. These latter substrates were hydrogenated selectively to the carbamates of the allyl alcohol.
- Panella, Lavinia,Feringa, Ben L.,De Vries, Johannes G.,Minnaard, Adriaan J.
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p. 4177 - 4180
(2007/10/03)
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- Highly compatible metal and enzyme catalysts for efficient dynamic kinetic resolution of alcohols at ambient temperature
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(Chemical equation presented). The combination of highly compatible metal and enzyme catalysts allows the fastest dynamic kinetic resolution of alcohols ever reported. The use of ruthenium catalyst 1a (or 1b) and an immobilized lipase results in a highly
- Martin-Matute, Belen,Edin, Michaela,Bogar, Krisztian,Baeckvall, Jan-E.
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p. 6535 - 6539
(2007/10/03)
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- Asymmetric hydrogenation of itaconic acid and enol acetate derivatives with the Rh-TangPhos catalyst
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(Matrix presented) The Rh-TangPhos catalyst has been used for asymmetric hydrogenation of itaconic acid and enol acetate derivatives. A variety of chiral 2-substituted succinic acids and chiral acetates have been obtained in excellent ee values (up to 99% ee).
- Tang, Wenjun,Liu, Duan,Zhang, Xumu
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p. 205 - 207
(2007/10/03)
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- One-pot lipase-catalyzed synthesis of enantiopure secondary alcohols from carbonyl compounds: A new protocol for lipase-mediated resolution
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Reduction of acetophenones with sodium borohydride in the presence of neutral alumina in hexane followed by enantioselective acylation catalyzed by Pseudomonas cepacia lipase has been achieved in one-pot. Further, immobilized lipase offered a high degree of selectivity with spontaneity.
- Kamal, Ahmed,Sandbhor, Mahendra,Ramana
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p. 815 - 820
(2007/10/03)
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- Enantioselective acylation of primary and secondary alcohols catalyzed by lipase QL from Alcaligenes sp.: A predictive active site model for lipase QL to identify which enantiomer of an alcohol reacts faster in this acylation
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Lipase QL (from Alcaligenes sp.)-catalyzed acylation of alcohols using isopropenyl acetate as the acylating agent in diisopropyl ether converted preferentially primary alcohols with an S configuration and secondary alcohols with an R configuration into the corresponding homochiral acetates. On the basis of observed enantiomer selectivities, a predictive active site model for lipase QL is proposed for identifying which enantiomer of a primary or a secondary alcohol reacts faster in this acylation. Copyright (C) 1996 Published by Elsevier Science Ltd.
- Naemura, Koichiro,Murata, Masaki,Tanaka, Rie,Yano, Masashi,Hirose, Keiji,Tobe, Yoshito
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p. 3285 - 3294
(2007/10/03)
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- Enantioselective acylation of alcohols catalyzed by lipase QL from Alcaligenes sp.: A predictive active site model for lipase QL to identify the faster reacting enantiomer of an alcohol in this acylation
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Lipase QL-catalyzed acylation of secondary alcohols using isopropenyl acetate as the acylating agent in diisopropyl ether gave preferentially the corresponding acetate with an R configuration. On the basis of the results, a predictive active site model for lipase QL is proposed for identifying which enantiomer of a secondary alcohol reacts faster in this reaction.
- Naemura,Murata,Tanaka,Yano,Hirose,Tobe
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p. 1581 - 1584
(2007/10/03)
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- Lipase-catalyzed enantioselective acylation of alcohols: A predictive active site model for lipase YS to identify which enantiomer of an alcohol reacts faster in this acylation
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Primary alcohols having a hydroxymethyl group at an S sterogemic center and secondary alcohols with an R configuration are preferentially acylated to give the corresponding acetates by lipase YS (from Pseudomonas fluorescens)-catalyzed acylation using isopropenyl acetate as the acylating agent in diisopropyl ether. On the basis of enantiomer selectivities observed, a predictive active site model for lipase YS is proposed for identifying which enantiomer of a primary or a secondary alcohol reacts faster in this acylation.
- Naemura,Fukuda,Murata,Konishi,Hirose,Tobe
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p. 2385 - 2394
(2007/10/03)
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- Lipase YS-catalysed Acylation of Alcohols: a Predictive Active Site Model for Lipase YS to Identify which Enantiomer of a Primary or a Secondary Alcohol Reacts Faster in this Acylation
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Primary alcohols having a hydroxymethyl group at an S chiral centre and secondary alcohols with an R configuration are preferentially acylated to give the corresponding acetates by lipase YS-catalysed acylation in diisopropyl ether; a predictive cubic-spaced active site model for lipase YS is proposed for identifying which enantiomer of a primary or a secondary alcohol reacts faster in this acylation.
- Naemura, Koichiro,Fukuda, Ritsuko,Konishi, Masayoshi,Hirose, Keiji,Tobe, Yoshito
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p. 1253 - 1256
(2007/10/02)
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- ASYMMETRIC ACYLATION OF ALCOHOLS IN THE PRESENCE OF CHIRAL TERTIARY AMINES
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The asymmetric acylation of secondary alcohols with acetic anhydride in the presence of chiral tertiary amines, synthesized from S-(-)-α-phenylethylamine, was investigated.The optical yield of the obtained alcohols was not greater than 2.4percent.It was established that in the presence of S-(-)-N,N-dimethyl-α-phenylethylamine the unreacted alcohol is rich in the S isomer.On the basis of this relationship the S configuration was proposed for (-)-4-iodo-, (-)-4-chloro-, and (-)-3-nitrophenylehanols.
- Potapov, V. M.,Dem'yanovich, V. M.,Khlebnikov, V. A.,Koval'skaya, S. S.
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p. 1602 - 1606
(2007/10/02)
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- Concerted Bimolecular Substitution Reactions of 1-Phenylethyl Derivatives
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Substituted 1-phenylethyl derivatives with ?+ > -0.08 exhibit bimolecular substitution reactions with azide ion in 20percent acetonitrile in water.The reactions with 1-phenylethyl chlorides follow a Hammett correlation with ρ = -2.9, compared with ρ = -5.6 (r+ = 1.15) for solvolysis.Swain-Scott correlations give values of s = 0.46 and 0.22 for 1-(4-nitrophenyl)ethyl chloride and tosylate, respectively; there are large positive deviations for azide ion and water and negative deviations for cyanide ion.The value of βnuc is 0.09 for reactions of substituted acetates with the chloride.The reactions exhibit ''synergism'' between the nucleophile and leaving group that favors the bimolecular reaction with Me2S, Br- > Cl- > OTs- leaving groups.The bimolecular reaction with azide follows the Grunwald-Winstein Y correlation with m = 0.8 in methanol-water mixtures.Bimolecular reactions with less reactive nucleophiles in the series N3-, CN-, AcO-, and ROH appear at progressively larger ? values, as the carbocation becomes less stable.It is concluded that these reactions are SN2 displacements that proceed through an open, ''exploded'' transition state that closely resembles a carbocation.Specific salt effects are small in water but are significant in acetonitrile-water mixtures and could be mistaken for normal or induced common ion rate depressions.No evidence was obtained for nucleophilic assistance to the formation of a carbocation intermediate.Concurrent SN1 and SN2 pathways occur in the reactions with solvent and azide of dimethylsulfonium ion, 1-(4-fluorophenyl)ethyl chloride, 1-(3-methoxyphenyl)ethyl chloride, and, probably, 1-(3-nitro-4-methoxyphenyl)ethyl chloride.Crude estimates of the lifetime of the carbocation intermediate in the presence of the nucleophile are consistent with the hypothesis that the concerted reactions are enforced by the absence of a significant lifetime of the carbocation in the presence of the nucleophile and that stepwise mechanisms are followed when the intermediate has a significant lifetime; the change from a stepwise to a concerted mechanism occurs when the intermediate ceases to have a lifetime in the presence of a nucleophile.
- Richard, John P.,Jencks, William P.
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p. 1383 - 1396
(2007/10/02)
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