- Asymmetric Hydrogenation in Water by a Rhodium Complex of Sulfonated 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (binap)
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The synthesis of sulfonated 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (binap) is reported; a rhodium complex of this ligand is the first to perform asymmetric hydrogenation in neat water with optical yields as high as those obtained in nonaqueous solvent.
- Wan, Kam-to,Davis, Mark E.
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Read Online
- Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
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Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
- Kwon, Hongmok,Ha, Hyunsoo,Jeon, Hayoung,Jang, Jaebong,Son, Sang-Hyun,Lee, Kiho,Park, Song-Kyu,Byun, Youngjoo
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supporting information
(2020/12/25)
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- The effect of imidazolium salts with amino acids as counterions on the reactivity of 4-nitrophenyl acetate: A kinetic study
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As a first approach to improve the “green character” of the surfactants based on imidazolium cations, three surfactants using 1-tetradecyl-3-methylimidazolium [C14mim]+ as cation and different amino acids (AA) as counterion, were syn
- Figueroa, Roberto,Orth, Elisa,Pavez, Paulina,Rojas, Mabel,Santos, José G.
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- GRANZYME B DIRECTED IMAGING AND THERAPY
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Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 108
(2019/09/04)
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- Oxidative Damage in Aliphatic Amino Acids and Di- and Tripeptides by the Environmental Free Radical Oxidant NO3?: the Role of the Amide Bond Revealed by Kinetic and Computational Studies
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Kinetic and computational data reveal a complex behavior of the important environmental free radical oxidant NO3? in its reactions with aliphatic amino acids and di- and tripeptides, suggesting that attack at the amide N-H bond in the peptide backbone is a highly viable pathway, which proceeds through a proton-coupled electron transfer (PCET) mechanism with a rate coefficient of about 1 × 106 M-1 s-1 in acetonitrile. Similar rate coefficients were determined for hydrogen abstraction from the α-carbon and from tertiary C-H bonds in the side chain. The obtained rate coefficients for the reaction of NO3? with aliphatic di- and tripeptides suggest that attack occurs at all of these sites in each individual amino acid residue, which makes aliphatic peptide sequences highly vulnerable to NO3?-induced oxidative damage. No evidence for amide neighboring group effects, which have previously been found to facilitate radical-induced side-chain damage in phenylalanine, was found for the reaction of NO3? with side chains in aliphatic peptides.
- Nathanael, Joses G.,Wille, Uta
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p. 3405 - 3418
(2019/03/11)
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- Kinetic resolution of N-acetyl-DL-alanine methyl ester using immobilized Escherichia coli cells bearing recombinant esterase from Bacillus cereus
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D-alanine is widely used in medicine, food, additives, cosmetics, and other consumer items. Esterase derived from Bacillus cereus WZZ001 exhibits high hydrolytic activity and stereoselectivity. In this study, we expressed the esterase gene in Escherichia coli BL21 (DE3). We analyzed the biocatalytic resolution of N-acetyl-DL-alanine methyl ester by immobilized whole E.?coli BL21 (DE3) cells, which were prepared through embedding and cross-linking. We analyzed biocatalytic resolution under the optimal conditions of pH of 7.0, temperature of 40°C and substrate concentration of at 700?mM with an enantiomeric excess of 99.99% and e.e.p of 99.50%. The immobilized recombinant B.?cereus esterase E.?coli BL21 (DE3) cells exhibited excellent reusability and retained 86.04% of their initial activity after 15 cycles of repeated reactions. The immobilized cells are efficient and stable biocatalysts for the preparation of N-acetyl-D-alanine methyl esters.
- Zheng, Jianyong,Lan, Xing,Huang, Lijuan,Zhang, Yinjun,Wang, Zhao
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p. 907 - 912
(2018/06/19)
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- Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H2O2 catalyzed by a nonheme imine based iron complex
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The oxidation of a series of N-acetyl amino acid methyl esters with H2O2 catalyzed by a very simple iminopyridine iron(ii) complex 1 easily obtainable in situ by self-assembly of 2-picolylaldehyde, 2-picolylamine, and Fe(OTf)2 was investigated. Oxidation of protected aliphatic amino acids occurs at the α-C-H bond exclusively (N-AcAlaOMe) or in competition with the side-chain functionalization (N-AcValOMe and N-AcLeuOMe). N-AcProOMe is smoothly and cleanly oxidized with high regioselectivity affording exclusively C-5 oxidation products. Remarkably, complex 1 is also able to catalyze the oxidation of the aromatic N-AcPheOMe. A marked preference for the aromatic ring hydroxylation over Cα-H and benzylic C-H oxidation was observed, leading to the clean formation of tyrosine and its phenolic isomers.
- Ticconi, Barbara,Colcerasa, Arianna,Di Stefano, Stefano,Lanzalunga, Osvaldo,Lapi, Andrea,Mazzonna, Marco,Olivo, Giorgio
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p. 19144 - 19151
(2018/05/31)
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- Rapid Room-Temperature Gelation of Crude Oils by a Wetted Powder Gelator
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Phase-selective organogelators (PSOGs) not only exhibit ability to phase-selectively congeal oil from oily water but also allow easy separation of gelled oil from the body of water. However, all hitherto reported PSOGs either necessitate carrier solvents for their dissolution or suffer from an extremely slow action in gelling oil in the powder form. A previously unexplored generally applicable wetting strategy is now described to dramatically enhance, by up to two orders of magnitude, gelling speed of the resultant wet but non-sticky gelator in the powder form in crude oils of widely ranging viscosities. Such unprecedented rapid gelling speeds enable rapid gelation of six types of (un)weathered crude oils within minutes at room temperature, making PSOGs one step closer to their eventual practical uses as one of important oil spill control technologies.
- Ren, Changliang,Shen, Jie,Chen, Feng,Zeng, Huaqiang
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supporting information
p. 3847 - 3851
(2017/03/27)
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- KetoABNO/NOx Cocatalytic Aerobic Oxidation of Aldehydes to Carboxylic Acids and Access to α-Chiral Carboxylic Acids via Sequential Asymmetric Hydroformylation/Oxidation
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A method for aerobic oxidation of aldehydes to carboxylic acids has been developed using organic nitroxyl and NOx cocatalysts. KetoABNO (9-azabicyclo[3.3.1]nonan-3-one N-oxyl) and NaNO2 were identified as the optimal nitroxyl and NOx sources, respectively. The mildness of the reaction conditions enables sequential asymmetric hydroformylation of alkenes/aerobic aldehyde oxidation to access α-chiral carboxylic acids without racemization. The scope, utility, and limitations of the oxidation method are further evaluated with a series of achiral aldehydes bearing diverse functional groups.
- Miles, Kelsey C.,Abrams, M. Leigh,Landis, Clark R.,Stahl, Shannon S.
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supporting information
p. 3590 - 3593
(2016/08/16)
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- Absolute configuration of iminimycin B, a new indolizidine alkaloid, from Streptomyces griseus OS-3601
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Iminimycin B, a novel indolizine alkaloid featuring a rare pyridinium, was isolated from the cultured broth of a streptomycin-producing strain, Streptomyces griseus OS-3601, through a physicochemical screening method. Its structure was elucidated on the basis of mass and NMR analyses. Stereochemical assignment of iminimycin B was archived by NMR studies, electronic circular dichroism (ECD) analysis, and advanced Marfey's method.
- Nakashima, Takuji,Miyano, Rei,Matsuo, Hirotaka,Iwatsuki, Masato,Shirahata, Tatsuya,Kobayashi, Yoshinori,Shiomi, Kazuro,Petersson, George A.,Takahashi, Yōko,ōmura, Satoshi
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supporting information
p. 3284 - 3286
(2016/07/11)
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- Energetic contribution to both acidity and conformational stability in peptide models
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The acidity of N-acyl amino acids is dependent upon the rotameric state of the amide bond. In this work we systematically investigated the acidity difference of the rotamers (ΔpKa) in the frames of various acetylated amino acids. Our results indicated a mutual interaction of two carbonyl groups of an attractive type. We observed conservative ΔpKas for acyclic amino acids (2.2-3.0 kJ mol-1), whereas in the case of alicyclic amino acids, the experimental values revealed a strong dependency on the structural context (1.5-4.4 kJ mol-1). In homologous amino acids (α-, β-, γ-, etc.), the strength of the attraction decays in an exponential fashion. Furthermore, the interaction can accumulate through a chain of amide bonds in a cascade fashion, as demonstrated by an Ac-Pro-Pro dipeptide. As a result, we demonstrate that ΔpKa is an experimental parameter to estimate increments in the carbonyl-carbonyl alignment, as determined by the amino acid or peptidyl context. This parameter is also important in understanding the roles of amino acids in both protein folding and translation in biological systems as well as their evolutionary appearance in the genetic code.
- Kubyshkin, Vladimir,Durkin, Patrick,Budisa, Nediljko
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supporting information
p. 5209 - 5220
(2016/07/06)
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- Peptide Tyrosinase Activators
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Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
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- Pinene-derived monodentate phosphoramidites for asymmetric hydrogenation
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Phosphoramidite ligands based on pinene-derived chiral amines have been prepared by a straightforward procedure in good yields. The key step of the synthetic protocol is a stereoselective hydrogenation of annulated pinene-pyridine derivatives leading to (diastereoisomeric) secondary amines that were separated and treated with different chlorophosphites to yield the envisaged phosphoramidites. The absolute configurations of the ligands were assigned on the basis of NMR analyses and corroborated by X-ray diffraction analysis of a borane adduct of a typical ligand. The new ligands were employed in the asymmetric hydrogenation of imines and olefins. The iridium-catalyzed hydrogenation of imines provided up to 81?% ee, whereas in the rhodium-catalyzed hydrogenation of functionalized olefins enantioselectivities of up to 99?% ee were achieved. In this particular application, the different chiral elements of the ligand structure led to synergistic effects and the enantioselectivity is dominated by the chiral diol moiety.
- Schmitz, Christian,Leitner, Walter,Franciò, Giancarlo
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p. 2889 - 2901
(2015/04/27)
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- Synthesis of phospholane-phosphoramidite ligands and their application in asymmetric catalysis
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A set of phospholane-phosphoramidite ligands, which possess four elements of chirality, has been synthesized through a modular diastereoselective process. The ligands were applied in the Rh-catalyzed asymmetric C =C hydrogenation of several functionalized olefins with enantioselectivities of up to 99 % ee and a turnover frequency of up to 12 000 h-1, in the Rh-catalyzed hydroformylation of vinyl arenes with enantioselectivities of up to 79 % ee, and in the Ir-catalyzed asymmetric C =N hydrogenation of different aryl imines with enantioselectivities of up to 79 % ee. New P,P′ hybrid ligands: A set of phospholane-phosphoramidites (quinaphoslane) with four elements of chirality are synthesized through a modular diastereoselective process and applied in the Rh-catalyzed hydrogenation of functionalized olefins with up to 99 % ee and a turnover frequency (TOF) of up to 12 000 h-1, in the Rh-catalyzed hydroformylation of vinyl arenes with regioselectivities of up to 99 % and up to 79 % ee, and in the Ir-catalyzed hydrogenation of imines with up to 79 % ee.
- Hammerer, Tim,Leitner, Walter,Franciò, Giancarlo
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p. 1583 - 1592
(2015/05/27)
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- Aqueous MW eco-friendly protocol for amino group protection
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In this paper a new catalyst-free and on-water method for protection of amines and amino acids with di-tert-butyl dicarbonate, 9-fluorenylmethoxycarbonyl chloride, acetyl chloride and tosyl chloride is presented. The protection can be realized in a few minutes under microwave-assistance. The reaction proved to be chemoselective in presence of ambident nucleophiles and water solution of di-tert-butyl carboxylic acid or chloride acid are the only wastes produced.
- Nardi,Cano, N. Herrera,Costanzo,Oliverio,Sindona,Procopio
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p. 18751 - 18760
(2015/06/15)
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- "Backdoor Induction" of chirality in asymmetric hydrogenation with rhodium(I) complexes of amino acid substituted triphenylphosphane ligands
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This paper describes the synthesis and characterization of 5-(diphenylphosphanyl)isophthalic acid bioconjugates (Lig-[R]2). In addition to symmetrically disubstituted conjugates with amino acids, peptides or amines, a convenient one-pot, two-step procedure for the synthesis of conjugates bearing two different substituents is reported. The 28 prepared phosphanes were used as monodentate ligands in the rhodium(I)-catalyzed hydrogenation of 2-acetamidoacrylate and (Z)-α-acetamidocinnamate. The ligand with the smallest side-chain substituents Lig-[Ala-OMe]2 (1a) revealed the highest selectivity, with up to 84 % ee. The catalysts presented herein are models of artificial metalloenzymes in which the outer-coordination sphere controls the selectivity in catalysis. The chirality of distant hydrogen-bonded amino acids is transmitted by "backdoor induction" to the prochiral RhI center. Models of artificial metalloenzymes are presented in which the outer-coordination sphere controls the selectivity in catalysis. The chirality of distant hydrogen-bonded amino acids or amines is transmitted by "backdoor induction" to the prochiral RhI center. Copyright
- Kokan, Zoran,Kirin, Srecko I.
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supporting information
p. 8154 - 8161
(2014/01/06)
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- Synthesis of Binol-based diphosphinites bearing chiral phospholane units and their application in asymmetric catalysis
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New diphosphinite ligands based on atropoisomeric diol backbones and (R,R)-2,5-dimethylphospholane moieties have been prepared and fully characterised. For each ligand structure, both diastereomers have been synthesised. These ligands are available through a straightforward procedure in good yields. The solid state structures of two diastereomeric ligands are reported. These ligands have been applied to Rh-catalysed asymmetric hydrogenations and hydroformylations of CC bonds as well as in Ir-catalysed asymmetric hydrogenations of CN bonds. Turnover frequencies in the range of 10,000 h-1 and enantioselectivities of up to 98% ee have been achieved. The different chirality elements within the ligands led to marked cooperative effect in catalysis. Interestingly, there is no general privileged diastereomeric structure but rather a matched diastereomer for each application.
- Hammerer, Tim,Weisgerber, Laurent,Schenk, Stefan,Stelzer, Othmar,Englert, Ulli,Leitner, Walter,Franci, Giancarlo
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experimental part
p. 53 - 59
(2012/05/20)
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- 3,3′-Substituted BINAP derivatives containing C-bound substituents: Applications in asymmetric hydrogenation reactions
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The synthesis and resolution of the first 3,3′-disubstituted BINAP ligands containing C-bonded substituents are described. An ortho-metallation/ electrophile capture sequence was used to obtain the key trisubstituted naphthalene intermediate available and this intermediate was successfully converted into the desired ligands. Minor changes in the steric and stereoelectronic components of the 3,3′-substituents on the enantioselectivity and product enantiosense were also assessed in the context of the Rh-catalyzed asymmetric hydrogenation of enamides. A comparison of the absolute stereochemistry of the products derived from 3,3′-disubstituted BINAPs containing C-bonded substituents with their O-bound counterparts indicated that the product enantiosense could be dictated by increased steric bulk due to the 3 and 3′-substituents.
- Rankic, Danica A.,Parvez, Masood,Keay, Brian A.
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experimental part
p. 754 - 763
(2012/09/05)
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- Synthesis of novel chiral monophosphine ligands derived from isomannide and isosorbide. Application to enantioselective hydrogenation of olefins
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A new class of monophosphine ligands has been prepared from natural chirality renewable source, 1,4:3,6-dianhydrohexitol compounds, via a nucleophilic substitution process, or a hydrophosphination reaction involving microwave activation. These ligands have been evaluated for the rhodium-catalyzed enantioselective hydrogenation of olefins giving good conversion and enantioselectivity up to 95% and 96% ee, respectively.
- Ibrahim, Houssein,Bournaud, Chloée,Guillot, Régis,Toffano, Martial,Vo-Thanh, Giang
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scheme or table
p. 4900 - 4902
(2012/09/21)
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- Reactions of substituted aspirins with amino acids
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Acyl transfers are key reactions in biology and in the laboratory. In biological systems they are involved in energy transport, in the assembly of complex molecules and in the mechanisms of efficient action of many hydrolytic enzymes. We report a mechanistic and calculational study of the selective N-acylation reactions of amino acids by substituted aspirins, under mild conditions, in water at 25 °C. The acetylated amino-acid products of the reactions were identified by nuclear magnetic resonance, and the reaction steps were studied by density functional theory. Copyright
- Orth, Elisa S.,Medeiros, Michelle,Souza, Bruno S.,Caon, Natalia B.,Kirby, Anthony J.,Nome, Faruk
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supporting information
p. 939 - 945
(2014/01/06)
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- Organocatalytic asymmetric tandem condensation-intramolecular rearrangement-protonation: An approach to optically active α-amino thioester derivatives
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An unprecedented and conceptually novel chiral Bronsted base/Bronsted acid catalytic method for the enantioselective synthesis of α-amino thioesters through a tandem condensation-intramolecular rearrangement-protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities.
- Capitta, Francesca,Frongia, Angelo,Piras, Pier Paolo,Pitzanti, Patrizia,Secci, Francesco
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supporting information; scheme or table
p. 490 - 494
(2012/01/15)
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- Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition
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The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides has been achieved. These new chiral diphosphine ligands could be employed as a ligand for the rhodiumcatalyzed asymmetric catalyses.
- Mori, Fumiya,Fukawa, Naohiro,Noguchi, Keiichi,Tanaka, Ken
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supporting information; experimental part
p. 362 - 365
(2011/04/16)
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- Design and synthesis of a novel three-hindered quadrant bisphosphine ligand and its application in asymmetric hydrogenation
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A novel three hindered quadrant bisphosphine ligand has been synthesized. The ligand shows excellent enantioselectivities and reactivities for rhodium-catalyzed hydrogenations of various functionalized olefins.
- Huang, Kexuan,Zhang, Xiaowei,Emge, Thomas J.,Hou, Guohua,Cao, Bonan,Zhang, Xumu
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supporting information; experimental part
p. 8555 - 8557
(2011/01/03)
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- DiPAMP's big brother "i-Pr-SMS-Phos" exhibits exceptional features enhancing rhodium(I)-catalyzed hydrogenation of olefins
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Switching Knowles DiPAMP's {DiPAMP = l,2-bis[(o-anisyl)(phenyl)phosphino] ethane} MeO groups with i-PrO ones led to the iPr-SMS-Phos {i-Pr-SMS-Phos = l,2-bis[(o-isopropoxyphenyl)(phenyl)phosphino]ethane} ligand which displayed a boosted catalyst activity coupled with an enhanced enantioselectivity in the rhodium(I)catalyzed hydrogenation of a wide-range of representative olefinic substrates (dehydro-a-amido acids, itaconates, acrylates, enamides, enol acetates, α,α-diarylethylenes, etc). The rhodium(I)-(i-PrSMS-Phos) catalytic profile was investigated revealing its structural attributes and robustness, and in contrast to the usual trend, 31P NMR analysis revealed that its methyl (Z)-α-acetamidocinnamate (MAC) adduct consisted of a reversed diastereomeric ratio of 1.4:1 in favour of the most reactive diastereomer.
- Stephan, Michel,Sterk, Damjan,Mohar, Barbara
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supporting information; scheme or table
p. 2779 - 2786
(2010/03/25)
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- A new method proposed for the determination of absolute configurations of α-amino acids
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Enantiopure α-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl3, an equimolar amount of the chiral dirhodium complex Rh2(II)[(R)-(+)-MTPA]4 (MTPA-H = Mosher's acid) was added, and the 1H NMR spectra of the resulting samples were recorded [dirhodium method). The relative intensities of 1H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting a-amino acids. Binding atoms in the adducts were identified by comparing the 1H and 13C chemical shifts of the oxazolones in the absence and presence of Rh2(II)[(R)-(+)- MTPA]4. Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented. Copyright
- Gomez, Edison Diaz,Duddeck, Helmut
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experimental part
p. 222 - 227
(2010/02/28)
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- Towards an efficient prodrug of the alkylating metabolite monomethyltriazene: Synthesis and stability of N-acylamino acid derivatives of triazenes
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A series of 3-[α-(acylamino)acyl]-1-aryl-3-methyltriazenes 6a-l, potential cytotoxic triazene prodrugs, were synthesised by coupling 1-aryl-3-methyltriazenes to N-acylamino acids. Their hydrolysis was studied in isotonic pH 7.4 phosphate buffer and in hum
- Perry, Maria de Jesus,Carvalho, Emilia,Rosa, Eduarda,Iley, Jim
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scheme or table
p. 1049 - 1056
(2009/08/14)
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- Lipase activity of Lecitase Ultra: characterization and applications in enantioselective reactions
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The general properties of Lecitase Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca2+ and Mg2+ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer (E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity (E = 1-5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate (E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2S,3R)-enantiomer providing unreacted (2R,3S)-glycidate esters (ee >99%, conversion 52-55%) by the immobilized enzyme.
- Mishra, Mithilesh Kumar,Kumaraguru, Thenkrishnan,Sheelu, Gurrala,Fadnavis, Nitin W.
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experimental part
p. 2854 - 2860
(2010/04/05)
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- Thioesterase-like role for fungal PKS-NRPS hybrid reductive domains
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Fungal reduced polyketides possess diverse structures exploring a broad region of chemical space despite their synthesis by very similar enzymes. Many fungal polyketides are capped by diverse amino acid-derived five-membered rings, the tetramic acids and related pyrrolidine-2-ones. The known tetramic acid synthetase enzymes in fungi contain C-terminal reductive (R) domains that were proposed to release reduced pyrrolidine-2-one intermediates en route to the tetramic acids. To determine the enzymatic basis of pyrrolidine-2-one diversity, we overexpressed equisetin synthetase (EqiS) R domains and analyzed their reactivity with synthetic substrate analogs. We show that the EqiS R domain does not perform a reducing function and does not bind reducing cofactors. Instead, the EqiS R catalyzes a Dieckmann condensation, with an estimated kcat ≈ 15 s-1. This role differs from the redox reactions normally catalyzed by short chain dehydrogenase/reductase superfamily enzymes.
- Sims, James W.,Schmidt, Eric W.
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supporting information; experimental part
p. 11149 - 11155
(2009/02/05)
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- Enantioselective hydrogenation of N-acetyldehydroamino acids over supported palladium catalysts
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The enantioselective hydrogenation of two N-acetyldehydroamino acids over Cinchona alkaloid-modified, supported palladium catalysts has been studied. Moderate enantioselectivities, up to 36%, were obtained in the hydrogenation of 2-acetamidocinnamic acid over cinchonidine-modified Pd/TiO2 under low hydrogen pressure. Increase in the pressure or use of benzylamine as additive led to a gradual decrease in the enantiomeric excess and eventually inversion of the sense of the enantioselectivity. On the contrary, the optical purity of the product resulting from the hydrogenation of 2-acetamidoacrylic acid was significantly increased by addition of benzylamine to the reaction mixture. Enantiomeric excess values up to 58% and 60% were obtained over Pd/Al 2O3 modified by cinchonidine and cinchonine, respectively. These optical purities are the best obtained in the hydrogenation of dehydroamino acid derivatives over chirally modified heterogeneous metal catalysts.
- Szoellosi, Gyoergy,Szabo, Emese,Barto, Mihaly
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p. 405 - 410
(2008/02/07)
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- BISPHOSPHOLANES FOR USE AS CATALYSTS IN ASYMMETRIC REACTIONS
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The invention is a set of novel bisphospholane ligands that can be complexed with transition metals. These complexes are useful as catalysts in asymmetric reactions such as asymmetric hydrogenation.
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Page/Page column 33
(2008/06/13)
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- Novel phosphine ligands
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The invention is concerned with new phosphine ligands of the formula I wherein R1 and R2 are independently of each other alkyl, aryl, cycloalkyl or heteroaryl, said alkyl, aryl, cycloalkyl or heteroaryl may be substituted by alkyl, alkoxy, halogen, hydroxy, amino, mono- or dialkylamino, aryl, —SO2—R7, —SO3?, —CO—NR8R8′, carboxy, alkoxycarbonyl, trialkylsilyl, diarylalkylsilyl, dialkylarylsilyl or triarylsilyl; R3 is alkyl, cycloalkyl, aryl or heteroaryl; R4′ and R4 signify independently of each other hydrogen, alkyl or optionally substituted aryl; or R4′ and R4 together with the C-atom they are attached to form a 3-8-membered carbocyclic ring; dotted line is absent or is present and forms a double bond; R5 and R6 are independently of each other hydrogen, alkyl or aryl; or linked together to form a 3-8-membered carbocyclic ring or an aromatic ring; R7 is alkyl, aryl or NR8R8′; and R8 and R8′ are independently of each other hydrogen, alkyl or aryl; metal complexes with such ligands as well as the use of such metal complexes as catalysts in asymmetric reactions.
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Page/Page column 23-24
(2010/11/27)
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- 1,2-Bis(2,5-diphenylphospholano)methane, a new ligand for asymmetric hydrogenation
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1,2-Bis(2,5-diphenylphospholano)methane (Ph-BPM) has been prepared in good yield from 2,5-trans-diphenylphospholane-borane adduct. Rhodium and ruthenium complexes of this ligand have been prepared and their usefulness in asymmetric hydrogenation has been investigated. [Ph-BPM Rh(COD)]BF4 showed high activity and selectivity for itaconate and dehydroamino acid hydrogenation. Ph-BPM RuCl2(DPEN) was effective for imine hydrogenation.
- Jackson, Mark,Lennon, Ian C.
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p. 1831 - 1834
(2008/02/05)
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- Second generation artificial hydrogenases based on the biotin-avidin technology: Improving activity, stability and selectivity by introduction of enantiopure amino acid spacers
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We report on our efforts to create efficient artificial metalloenzymes for the enantioselective hydrogenation of N-protected dehydroamino acids using either avidin or streptavidin as host proteins. Introduction of chiral amino acid spacers - phenylalanine or proline - between the biotin anchor and the flexible aminodiphosphine moiety 1, combined with saturation mutagenesis at position S112X of streptavidin, affords second generation artificial hydrogenases displaying improved organic solvent tolerance, reaction rates (3-fold) and (S)-selectivities (up to 95% ee for N-acetamidoalanine and N-acetamidophenylalanine). It is shown that these artificial metalloenzymes follow Michaelis-Menten kinetics with an increased affinity for the substrate and a higher kcat than the protein-free catalyst (compare k cat 3.06 min-1 and KM 7.38 mM for [Rh(COD)Biot-1]+ with kcat 12.30 min-1 and KM 4.36 mM for [Rh-(COD)Biot-(R)-Pro-1]+ ? WT Sav). Finally, we present a straightforward protocol using Biotin-Sepharose to immobilize artificial metalloenzymes (> 92% ee for N-acetamidoalanine and N-acetamidophenylalanine using [Rh(COD)Biot-(R)-Pro-1]+ ? Sav S112W).
- Rusbandi, Untung E.,Lo, Cheikh,Skander, Myriem,Ivanova, Anita,Creus, Marc,Humbert, Nicolas,Ward, Thomas R.
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p. 1923 - 1930
(2008/09/18)
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- A one-pot enantioselective chemo-enzymatic synthesis of amino acids in water
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The combination of immobilised Rh-Mono-Phos (1-AlTUD-1) and acylase I afforded a chemoenzymatic, one-pot process for the enantioselective synthesis of amino acids in water, without the need for isolation of intermediates. In addition, the enzymatic hydrolysis increases the enantiopurity of the product from 95% ee to >98% ee. Compatibility studies revealed that for optimum results compartmentalisation of the catalysts is required.
- Simons, Chretien,Hanefeld, Ulf,Arends, Isabel W. C. E.,Maschmeyer, Thomas,Sheldon, Roger A.
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p. 471 - 475
(2007/10/03)
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- Synthesis of a novel spiro bisphosphinite ligand and its application in Rh-catalyzed asymmetric hydrogenation
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A novel, chiral bisphosphinite ligand (R)-SpiroBIP has been synthesized. The rhodium complex of the ligand was found to be highly enantioselective in the asymmetric hydrogenation of α-dehydroamino acid derivatives.
- Guo, Zhenqiu,Guan, Xiaoyu,Chen, Zhiyong
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p. 468 - 473
(2007/10/03)
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- PegPhos: A monodentate phosphoramidite ligand for enantioselective rhodium-catalysed hydrogenation in water
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A BICOL derived monodentate phosphoramidite ligand gives ee's up to 89% in the enantioselective Rh-catalysed hydrogenation of N-acyl dehydroalanine using water as the solvent. The Royal Society of Chemistry.
- Hoen, Rob,Leleu, Stephane,Botman, Peter N. M.,Appelman, Vanessa A. M.,Feringa, Ben L.,Hiemstra, Henk,Minnaard, Adriaan J.,Van Maarseveen, Jan H.
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p. 613 - 615
(2007/10/03)
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- Asymmetric hydrogenation with antibody-achiral rhodium complex
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An asymmetric hydrogenation of an amino acid precursor was catalyzed by the rhodium cyclooctadiene phosphine complex of a transition metal with immunoglobin. The hapten was covalently attached to a limpet hemocyanin (KLH) or bovine serum albumin (BSA) through activation of the carboxyl group in the hapten molecule using carbonyldiimidazole. The conjugates KLH-1 and BSA-1 were purified by size exclusion chromatography and used as an antigen to immunize mice and in enzyme linked immunosorbent assay (ELISA). The Rh complex was added to the aqueous solution of the monoclonal antibody under argon atmosphere at room temperature. It was found that the antibody IG8 could bind substrate than the hapten molecules, and the antibody IG8-Rh complex is stereoselective catalyst with substrate specificity through second sphere coordination.
- Yamaguchi, Hiroyasu,Hirano, Tohko,Kiminami, Hideaki,Taura, Daisuke,Harada, Akira
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p. 3571 - 3573
(2008/10/09)
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- Avoiding the classical resolution during the synthesis of MeO-BIPHEP and 3,3′-disubstituted derivatives
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The Ullmann coupling of 1 (R = H) gives a 2:1 mixture of diastereomers 2 (R = H) in 81% yield that are easily separated by silica gel chromatography. This procedure avoids the generally cumbersome and sometimes difficult resolution step with DBTA. Similar Ullmann couplings and separation of the corresponding diastereomers are employed with other derivatives of 1 (R = OtBu, iPr, Ph, and mesityl) ultimately affording a new series of 3,3′-disubsituted-MeO-BIPHEP derivatives. The use of these new derivatives in palladium-catalyzed asymmetric Heck reaction, Pd-catalyzed polyene cyclizations and rhodium-catalyzed hydrogenations is also reported.
- Gorobets, Evgueni,Wheatley, Bronwen M. M.,Hopkins, J. Matthew,McDonald, Robert,Keay, Brian A.
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p. 3843 - 3846
(2007/10/03)
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- Rh-catalyzed asymmetric hydrogenation of prochiral olefins with a dynamic library of chiral TROPOS phosphorus ligands
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A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium-catalyzed asymmetric hydrogenation of dehydro-α-amino acids, dehydro-β-amino acids, enamides and dimethyl itaconate. ee values up to 98% were obtained for the dehydro-α-amino acids, by using the best combination of ligands, a phosphite [4-P(O)2O] and a phosphora midite [13-P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4-P(O)2O] and phosphoramidite [13-P(O) 2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2-acetamidoacrylate and methyl 2-acetamidocinnamate faster than the mixture of the same phosphite with the phosphoramidite, while the phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/ phosphoramidite ratio is also presented.
- Monti, Chiara,Gennari, Cesare,Piarulli, Umberto,De Vries, Johannes G.,De Vries, Andre H. M.,Lefort, Laurent
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p. 6701 - 6717
(2007/10/03)
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- Chemical optimization of artificial metalloenzymes based on the biotin-avidin technology: (S)-selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers
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Incorporation of biotinylated-[rhodium(diphosphine)]+ complexes, with enantiopure amino acid spacers, in streptavidin affords solvent-tolerant and selective artificial metalloenzymes: up to 91% ee (S) in the hydrogenation of N-protected dehydroamino acids. The Royal Society of Chemistry 2005.
- Skander, Myriem,Malan, Christophe,Ivanova, Anita,Ward, Thomas R.
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p. 4815 - 4817
(2008/01/27)
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- A versatile synthesis of phosphine-aminophosphine ligands for asymmetric catalysis
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A new and versatile synthesis of phosphine-aminophosphine ligands allows the incorporation of a wide range of nitrogen and phosphorus substituents into these ligands, several of which exhibit improved properties for rhodium-catalyzed asymmetric hydrogenation reactions. This synthesis also allows the preparation of mixed phosphine-phosphoramidite species.
- Boaz, Neil W.,Ponasik Jr., James A.,Large, Shannon E.
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p. 2063 - 2066
(2007/10/03)
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- Synthesis and application of phosphinoferrocenylaminophosphine ligands for asymmetric catalysis
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(Chemical Equation Presented) A new class of bidentate ligands utilizing a phosphine-aminophosphine structure has been prepared on a ferrocenylethyl backbone in a straightforward and scalable fashion from acetylferrocene. The unique property of the α-ferrocenyl carbonium ion that allows the replacement of a variety of "leaving groups" with retention of configuration greatly facilitates the synthesis, and a number of ligands have been prepared by varying the nitrogen and phosphorus substituents on the aminophosphine. These readily prepared phosphinoferrocenylaminophosphines, known as BoPhoz ligands, show surprising hydrolytic and air stability, with no degradation after 3 years open to the air. The rhodium complexes of these ligands show exceedingly high enantioselectivities (generally > 95% ee) and activities often in excess of 50 000 catalyst turnovers per hour for the asymmetric hydrogenation of a wide variety of dehydro-α-amino acid and itaconic acid derivatives. They also show high activity and good to excellent enantioselectivity for the hydrogenation of a number of α-ketoesters.
- Boaz, Neil W.,Mackenzie, Elaine B.,Debenham, Sheryl D.,Large, Shannon E.,Ponasik Jr., James A.
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p. 1872 - 1880
(2007/10/03)
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- 3,3′-disubstituted BINAP ligands: Synthesis, resolution, and applications in asymmetric hydrogenation
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(Chemical Equation Presented) A novel family of BINAP ligands were prepared with alkoxy- and acetoxy-derived substituents in the 3,3′-positions. They were prepared through a convergent synthesis starting from readily available 4-bromo-2-naphthol. These ligands afforded excellent enantioselectivities in the asymmetric hydrogenation of substituted olefins. The presence of the 3,3′-substituents was shown to be beneficial by a direct comparison with the parent unsubstituted BINAP.
- Hopkins, J. Matthew,Dalrymple, Sean A.,Parvez, Masood,Keay, Brian A.
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p. 3765 - 3768
(2007/10/03)
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- Phosphine-phosphoramidite compounds
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Disclosed are novel phosphine-phosphoramidite compounds which may be employed in combination with a catalytically-active metal to effect a wide variety of reactions such as asymmetric hydrogenations, asymmetric reductions, asymmetric hydroborations, asymmetric olefin isomerizations, asymmetric hydrosilations, asymmetric allylations, asymmetric conjugate additions, and asymmetric organometallic additions. Also disclosed are a process for the preparation of the phosphine-phosphoramidite compounds, metal complex compounds comprising at least one of the phosphine-phosphoramidite compounds and a catalytically-active metal and hydrogenation processes utilizing the metal complex compounds.
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Page/Page column 14
(2010/02/11)
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- Preparation of aminophosphines
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Disclosed is a process for the preparation of phosphine-aminophosphines that are useful in the formation of catalysts useful in carrying out a wide variety of reactions such as asymmetric hydrogenations, asymmetric reductions, asymmetric hydroborations, asymmetric olefin isomerizations, asymmetric hydrosilations, asymmetric allylations, asymmetric conjugate additions, and asymmetric organometallic additions. The process comprises the steps of (1) contacting a compound of formula 2 [in-line-formulae]R2P—L—NHR3??2[/in-line-formulae] with phosphorus trihalide PX3 in the presence of an inert, organic solvent and an acid acceptor to produce intermediate compound having formula 3 (2) contacting intermediate compound 3 with a reactant having the formula R1—M1, R2—M1 or a mixture thereof.
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Page/Page column 16
(2010/02/11)
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- D-aminoacylase mutants
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The present invention provides mutant D-aminoacylases and use thereof. The mutant D-aminoacylases are hard to be inhibited by the substrate and, comprise the amino acid sequences of the D-aminoacylase derived from Alcaligenes denitrificans subsp. xylosoxydans MI-4 strain, wherein amino acid residues at specific sites have been modified. The mutants of the present invention have high reaction specificity as well as resistance to inhibition by the substrate. The present invention enables high-yield production of D-amino acids using higher concentrations of N-acyl-DL-amino acid as the substrate. The mutants of the present invention are useful in producing D-tryptophan in particular.
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- Synthesis of a novel spiro bisphosphinamidite ligand for highly enantioselective hydrogenation
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A novel chiral bisphosphinamidite ligand SpiroNP has been synthesized. The rhodium complex of this ligand has been found to be highly active and enantioselective in the asymmetric hydrogenation of (Z)-2-acetamidoacrylic acid derivatives and α,β-unsaturated carboxylic acid derivatives.
- Lin, Ching Wen,Lin, Chi-Ching,Lam, Louis F.-L.,Au-Yeung, Terry T.-L.,Chan, Albert S.C.
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p. 7379 - 7381
(2007/10/03)
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- Application of P-chirogenic bisphospholane ligands to rhodium catalyzed asymmetric hydrogenation of α- and β-acetamido dehydroamino acid derivatives
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Two previously reported P-chirogenic bisphospholane rhodium catalysts have been applied to the asymmetric hydrogenation of α- and β-acetamido dehydroamino acid derivatives. For α-acetamido dehydroamino acid derivatives, catalyst 4 produced very high enantiomeric excesses. These are contrasted with the previously reported enantiomeric excesses using catalyst 2. Both catalysts provide excellent enantioselectivity (96%) for the β-acetamido dehydroamino acid derivative, (E)-methyl 3-acetamido-2- butenoate. However, catalyst 2 produces higher enantioselectivity (89%) for the (Z)-isomer when compared to catalyst 4 (83%).
- Hoge, Garrett,Samas, Brian
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p. 2155 - 2157
(2007/10/03)
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- Artificial metalloenzymes: (Strept)avidin as host for enantioselective hydrogenation by achiral biotinylated rhodium-diphosphine complexes
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We report on the generation of artificial metalloenzymes based on the noncovalent incorporation of biotinylated rhodium-diphosphine complexes in (strept)avidin as host proteins. A chemogenetic optimization procedure allows one to optimize the enantioselectivity for the reduction of acetamidoacrylic acid (up to 96% ee (R) in streptavidin S112G and up to 80% ee (S) in WT avidin). The association constant between a prototypical cationic biotinylated rhodium-diphosphine catalyst precursor and the host proteins was determined at neutral pH: log Ka = 7.7 for avidin (pl = 10.4) and log Ka = 7.1 for streptavidin (pl = 6.4). It is shown that the optimal operating conditions for the enantioselective reduction are 5 bar at 30 °C with a 1% catalyst loading.
- Skander, Myriem,Humbert, Nicolas,Collot, Jerome,Gradinaru, Julieta,Klein, Gerard,Loosli, Andreas,Sauser, Jerome,Zocchi, Andrea,Gilardoni, Francois,Ward, Thomas R.
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p. 14411 - 14418
(2007/10/03)
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- Artificial metalloenzymes for enantioselective catalysis: The phenomenon of protein accelerated catalysis
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We report on the phenomenon of protein-accelerated catalysis in the field of artificial metalloenzymes based on the non-covalent incorporation of biotinylated rhodium-diphosphine complexes in (strept)avidin as host proteins. By incrementally varying the [Rh(COD)(Biot-1)]+ vs. (strept)avidin ratio, we show that the enantiomeric excess of the produced acetamidoalanine decreases slowly. This suggests that the catalyst inside (strept)avidin is more active than the catalyst outside the host protein. Both avidin and streptavidin display protein-accelerated catalysis as the protein embedded catalyst display 12.0- and 3.0-fold acceleration over the background reaction with a catalyst devoid of protein. Thus, these artificial metalloenzymes display an increase both in activity and in selectivity for the reduction of acetamidoacrylic acid.
- Collot, Jér?me,Humbert, Nicolas,Skander, Myriem,Klein, Gérard,Ward, Thomas R.
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p. 4868 - 4871
(2007/10/03)
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