38003-75-7Relevant academic research and scientific papers
An assay for DNA polymerase β lyase inhibitors that engage the catalytic nucleophile for binding
Chen, Shengxi,Cheng, Qi,Daskalova, Sasha M.,Eisenhauer, Brian M.,Fahmi, NourEddine,Feng, Xizhi,Gao, Mingxuan,Hecht, Sidney M.,Ji, Xun,Khdour, Omar M.
, (2020)
DNA polymerase β (Pol β) repairs cellular DNA damage. When such damage is inflicted upon the DNA in tumor cells treated with DNA targeted antitumor agents, Pol β thus diminishes their efficacy. Accordingly, this enzyme has long been a target for antitumor therapy. Although numerous inhibitors of the lyase activity of the enzyme have been reported, none has yet proven adequate for development as a therapeutic agent. In the present study, we developed a new strategy to identify lyase inhibitors that critically engage the lyase active site primary nucleophile Lys72 as part of the binding interface. This involves a parallel evaluation of the effect of the inhibitors on the wild-type DNA polymerase β (Pol β) and Pol β modified with a lysine analogue at position 72. A model panel of five structurally diverse lyase inhibitors identified in our previous studies (only one of which has been published) with unknown modes of binding were used for testing, and one compound, cis-9,10-epoxyoctadecanoic acid, was found to have the desired characteristics. This finding was further corroborated by in silico docking, demonstrating that the predominant mode of binding of the inhibitor involves an important electrostatic interaction between the oxygen atom of the epoxy group and Nε of the main catalytic nucleophile, Lys72. The strategy, which is designed to identify compounds that engage certain structural elements of the target enzyme, could find broader application for identification of ligands with predetermined sites of binding.
A stand-alone cobalt bis(dicarbollide) photoredox catalyst epoxidates alkenes in water at extremely low catalyst load
Guerrero, Isabel,Romero, Isabel,Teixidor, Francesc,Vi?as, Clara
, p. 10123 - 10131 (2021/12/27)
The cobalt bis(dicarbollide) complex, Na[3,3′-Co(η5-1,2-C2B9H11) (Na[1]), is an effective photoredox catalyst for the oxidation of alkenes to epoxides in water. Advantageous features of Na[1] include its lack of photoluminescence, high solubility and surfactant behavior in aqueous media, as well as the donor ability of the carborane ligand and high oxidizing power of the Co4+/3+ couple. These features differentiate it from the well-known and widely used photosensitizer tris (2,2′-bipyridine) ruthenium(ii) ([Ru(bpy)3]2+), which also participates in electron transfer through an outer sphere mechanism. A comparison of the catalytic performance of [Ru(bpy)3]2+ with Na[1] for alkene photo-oxidation is fully in favor of Na[1], as the former shows very low or null efficiency. With a catalyst loading of 0.1 mol% conversions between 65-97% have been obtained in short reaction times, 15 minutes, with moderate selectivity for the corresponding epoxide, due to the formation of side products as diols. But when the catalyst loading is reduced to 0.01 mol%, the selectivity for the corresponding epoxide increased considerably, being the only compound formed after 15 minutes of reaction (selectivity >99%). High TON values have been obtained (TON = 8500) for the epoxidation of aromatic and aliphatic alkenes in water. We have verified that Na[3,3′-Co(η5-1,2-C2B9H11)2] acts as a photocatalyst in both the epoxidation of alkenes and in their hydroxylation in aqueous medium with a higher rate for epoxidation than for hydroxylation. Preliminary photooxidation tests using methyl oleate as the substrate led to the selective epoxidation of the double bond. These results represent a promising starting point for the development of practical methods for the processing of unsaturated fatty acids, such as the valorisation of animal fat waste using this sustainable photoredox catalyst. This journal is
Synthesis of fatty ketoesters by tandem epoxidation-rearrangement with heterogeneous catalysis
Dorado, Vicente,Fraile, José M.,Gil, Lena,Herrerías, Clara I.,Mayoral, José A.
, p. 1789 - 1795 (2020/04/09)
Unsaturated fatty esters can be easily transformed into ketoesters through a two-step process. The highly efficient epoxidation is carried out with tert-butyl hydroperoxide (TBHP) in α,α,α-trifluorotoluene (TFT) using a Ti-silica heterogeneous catalyst. The formed epoxide is easily rearranged by a heterogeneous Br?nsted acid, with Nafion-silica SAC13 as the most efficient one. Both reactions can be combined in a tandem process, with separation of the Ti-silica catalyst by filtration from the reaction medium and addition of the second acid catalyst to perform the second reaction. Each catalyst is separated individually and can be reused, with or without re-activation, under the same conditions to maximize the productivity.
Tungstenocene-grafted silica catalysts for the selective epoxidation of alkenes
Bisio, Chiara,Gallo, Alessandro,Psaro, Rinaldo,Tiozzo, Cristina,Guidotti, Matteo,Carniato, Fabio
, p. 133 - 142 (2019/06/18)
Tungstenocene(IV) dichloride was successfully deposited and grafted on the surface of a commercially-available non-ordered silica support via either a liquid-phase or a dry impregnation approach. After a high-temperature calcination step, two W(VI)-grafted silica catalysts, with a metal loading around 1.2–1.7 wt.%, were obtained. They were fully characterized by physisorption and spectroscopic techniques, which evidenced well-dispersed tungsten oxide polyoxo cluster sites, for the catalyst prepared via liquid-phase grafting, and evenly dispersed larger monoclinic tungsten(VI) oxide aggregates, for the catalyst prepared via dry impregnation, respectively. Both W/SiO2 solids showed moderate to good conversion values in the epoxidation of (R)-(+)-limonene and methyl oleate (up to 68%), in the presence of aqueous hydrogen peroxide, with good selectivity to the desired epoxides (63% and 78%, respectively). The heterogeneous character of the most interesting W/SiO2 catalyst prepared via dry impregnation was confirmed by a hot centrifugation test and by an extended recovery and reuse of the solid in six catalytic runs.
Fatty acid based biocarbonates: Al-mediated stereoselective preparation of mono-, di- and tricarbonates under mild and solvent-less conditions
Pe?a Carrodeguas,Cristòfol,Fraile,Mayoral,Dorado,Herrerías,Kleij
supporting information, p. 3535 - 3541 (2017/08/15)
A catalytic method for the preparation of a series of fatty acid derived biocarbonates has been developed using a binary Al-complex/PPNCl catalyst. This catalyst system allows conversion of fatty acid derived epoxides under comparatively mild reaction conditions (70-85 °C, 10 bar) while maintaining high levels of diastereospecificity with cis/trans ratios of up to 97:3 in the products. The comparative catalysis data obtained for the reactions catalysed only by the nucleophilic halide based components show that the presence of the Al-complex is crucial for the retention of the original stereochemistry.
Allyl-Palladium-Catalyzed α,β-Dehydrogenation of Carboxylic Acids via Enediolates
Zhao, Yizhou,Chen, Yifeng,Newhouse, Timothy R.
supporting information, p. 13122 - 13125 (2017/09/13)
A highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2?2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches.
Cooperative catalyst system for the synthesis of oleochemical cyclic carbonates from CO2 and renewables
Tenhumberg, Nils,Büttner, Hendrik,Sch?ffner, Benjamin,Kruse, Daniela,Blumenstein, Michael,Werner, Thomas
supporting information, p. 3775 - 3788 (2016/07/07)
Phosphonium salts and various (transition-) metals were studied as catalysts in the synthesis of carbonated oleochemicals from the corresponding epoxides and carbon dioxide. In combination with tetra-n-butylphosphonium bromide molybdenum compounds were identified as highly active co-catalysts for the formation of cyclic carbonates. The co-catalyst accelerates the conversion of the epoxidized fatty acid ester considerably. The chemo- as well as the stereoselectivity of the carbonated oleochemicals can be controlled by the choice of the catalyst and the reaction conditions. Under optimized reaction conditions this new catalyst system allows the conversion of both mono- and polyepoxidized oleo compounds into the corresponding carbonates in good to excellent yields up to >99% under comparatively mild reaction conditions. This procedure has been applied to the synthesis of a potential renewable plasticizer and works well even at larger scale (200 g).
Mild catalytic oxidations of unsaturated fatty acid methyl esters (FAMEs) by oxovanadium complexes
Cecchini, Martina Maya,De Angelis, Francesco,Iacobucci, Claudio,Reale, Samantha,Crucianelli, Marcello
, p. 120 - 128 (2016/03/22)
A selection of unsaturated fatty acid methyl esters, namely methyl oleate (C18:1), methyl linoleate (C18:2) and methyl linolenate (C18:3) has been oxidized under mild homogeneous catalytic conditions, using a series of oxovanadium(IV) complexes containing 4-acyl-5-pyrazolone donor ligands with different substituents on acyl residue. The main goal was to evaluate the catalytic role exerted by oxovanadium(IV) metal center, as precursor complex, in the selective oxyfunctionalization of carbon-carbon double bonds of these bio-renewable resources, as a greener alternative to more drastic processes currently used at the industrial level. The three substrates, oxidized using tert-butylhydroperoxide as main oxidant, with or without solvents, showed high conversions of starting materials and high selectivities in the formation of corresponding mono- di- and tri-epoxides, especially under solvent-less conditions. Investigations on a probable catalytic cycle mechanism operative in the tert-butylhydroperoxide oxidation of a simple FAME model substrate, have been performed by means of ESI-MS.
Highly efficient nano-sized TS-1 with micro-/mesoporosity from desilication and recrystallization for the epoxidation of biodiesel with H2O2
Wilde,Pelz,Gebhardt,Gl?ser
, p. 3378 - 3389 (2015/06/25)
The epoxidation of the unsaturated fatty acid methyl esters (FAME) in biodiesel with H2O2 was investigated at 323 K in the liquid phase over microporous nano-sized TS-1 as well as micro-/mesoporous nano-sized TS-1. Nano-sized TS-1 with stacked morphology exhibits a catalytic activity per number of Ti sites up to 30% higher than a conventional, industrial TS-1 catalyst. Mesoporosity was successfully introduced by a desilication-recrystallization approach. Desilication by alkaline treatment in the presence of the structure-directing agent tetrapropylammonium cation (TPA+) or NaOH leads to the generation of undefined mesopores (10-40 nm), probably accompanied by an increase of the surface hydrophilicity. Consequently, the alkaline-treated materials show a two times lower catalytic activity in the epoxidation of biodiesel than the purely microporous parent material. The surfactant-assisted recrystallization of the alkaline-treated materials results in more uniform and smaller mesopores (3-10 nm). In the epoxidation, the recrystallized materials are remarkably more active with respect to both the purely microporous parent and alkaline-treated materials reaching a FAME conversion of 65% with an epoxide selectivity of 82%.
Substrate dependent synergetic and antagonistic interaction of ammonium halide and polyoxometalate catalysts in the synthesis of cyclic carbonates from oleochemical epoxides and CO2
Langanke, Jens,Greiner, Lasse,Leitner, Walter
, p. 1173 - 1182 (2013/06/27)
Organic halides and polyoxometalates (POMs) were studied as catalyst systems for the insertion of carbon dioxide into epoxides originating from plant oils as biogenic feedstock. In the formation of methyl oleate carbonate, synergistic rate acceleration and increased cis-selectivity were observed using ammonium halide and transition metal substituted silicotungstate POMs catalysts in a combined system. Mechanistic insight into the cooperative action was gained by kinetic measurements and analysis of the stereochemical outcome of the reaction. For poly-epoxidised oleochemicals as substrates, the simple ammonium halide catalyst gave better performance as side reactions were encountered with the POM-containing system.
