- Selective Functionalization of Aliphatic Amines via Myoglobin-Catalyzed Carbene N-H Insertion
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Engineered myoglobins have recently gained attention for their ability to catalyze a variety of abiological carbene transfer reactions including the functionalization of amines via carbene insertion into N-H bonds. However, the scope of myoglobin and other hemoprotein-based biocatalysts in the context of this transformation has been largely limited to aniline derivatives as the amine substrates and ethyl diazoacetate as the carbene donor reagent. In this report, we describe the development of an engineered myoglobin-based catalyst that is useful for promoting carbene N-H insertion reactions across a broad range of substituted benzylamines and α-diazo acetates with high efficiency (82-99percent conversion), elevated catalytic turnovers (up to 7,000), and excellent chemoselectivity for the desired single insertion product (up to 99percent). The scope of this transformation could be extended to cyclic aliphatic amines. These studies expand the biocatalytic toolbox available for the selective formation of C-N bonds, which are ubiquitous in many natural and synthetic bioactive compounds.
- Fasan, Rudi,Sreenilayam, Gopeekrishnan,Steck, Viktoria
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supporting information
p. 224 - 229
(2020/02/15)
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- Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA
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Some amino acid derivatives, such as R-glycine, have been synthesized together with their full spectroscopic characterization. The sodium salts of these bidentate amino acid ligands have been interacted with [M(bpy)(H2O)2](NO3)2 giving the corresponding some new complexes with formula [M(bpy)(R-gly)]NO3 (where M is Pt(II) or Pd(II), bpy is 2,2′-bipyridine and R-gly is butyl-, hexyl-and octyl-glycine). Due to less solubility of octyl derivatives, the biological activities of butyl and hexyl derivatives have been tested against chronic myelogenous leukemia cell line, K562. The interaction of these complexes with highly polymerized calf thymus DNA has been extensively studied by means of electronic absorption, fluorescence and other measurements. The experimental results suggest that these complexes positive cooperatively bind to DNA presumably via groove binding. Molecular dynamic results show that the DNA structure is largely maintained its native structure in hexylglycine derivative-water mixtures and at lower temperatures. The simulation data indicates that the more destabilizing effect of butylglycine is induced by preferential accumulation of these molecules around the DNA and due to their more negative free energy of binding via groove binding.
- Eslami Moghadam, Mahboube,Saidifar, Maryam,Divsalar, Adeleh,Mansouri-Torshizi, Hassan,Saboury, Ali Akbar,Farhangian, Hossein,Ghadamgahi, Maryam
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p. 203 - 219
(2016/01/20)
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- Tetramic acids as scaffolds: Synthesis, tautomeric and antibacterial behaviour
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Efficient synthetic routes for tetramic acids variously substituted on the ring nitrogen, their tautomeric behaviour in solution and their antibiotic activity are reported.
- Jeong, Yong-Chul,Moloney, Mark G.
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scheme or table
p. 2487 - 2491
(2010/03/01)
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- 5-Benzylidene-hydantoins: Synthesis and antiproliferative activity on A549 lung cancer cell line
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Benzylidene hydantoins have been recently reported as a new class of EGFR inhibitors. We describe here a simple and efficient methodology for the parallel solution-phase synthesis of a library of 5-benzylidene hydantoins, which were evaluated for antiproliferative activity on the human lung adenocarcinoma A549 cell line. Various substituents at positions 1, 3 and 5 on the hydantoin nucleus were examined. In the presence of a 5-benzylidene group and of a lipophilic substituent at position 1, most of the tested compounds inhibited cell proliferation at a concentration of 20 μM. Compound 7 (UPR1024), bearing 1-phenethyl and (E)-5-p-OH-benzylidene substituents, was found to be the most active derivative of the series. It inhibited EGFR autophosphorylation and induced DNA damage in A549 cells. Compound 7 and other synthesized 5-benzylidene hydantoin derivatives increased p53 levels, suggesting that the dual mechanism of action was a common feature shared by compound 7 and other member of the series.
- Zuliani, Valentina,Carmi, Caterina,Rivara, Mirko,Fantini, Marco,Lodola, Alessio,Vacondio, Federica,Bordi, Fabrizio,Plazzi, Pier Vincenzo,Cavazzoni, Andrea,Galetti, Maricla,Alfieri, Roberta R.,Petronini, Pier Giorgio,Mor, Marco
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experimental part
p. 3471 - 3479
(2009/12/24)
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- Invertible amphiphilic polymers
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Amphiphilic monomeric compounds and corresponding homopolymers and copolymers capable of assembly and invertible configuration in introduction to and change in fluid medium.
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Page/Page column 28
(2010/11/29)
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- Organic reactions catalyzed by methylrhenium trioxide: Reactions of ethyl diazoacetate and organic azides
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Methylrhenium trioxide (CH3ReO3 or MTO) catalyzes several classes of reactions of ethyl diazoacetate, EDA. It is the first high valent oxo complex for carbene transfer. Under mild conditions and in the absence of other substrates, EDA was converted to a 9:1 mixture of diethyl maleate and diethyl fumarate. In the presence of alcohols, α-alkoxy ethyl acetates were obtained in good yield. The yields dropped for the larger and more branched alcohols, the balance of material being diethyl maleate and fumarate. An electron-donating group in the para position of phenols favors the formation of α-phenoxy ethyl acetates. The use of EDA to form α-thio ethyl acetates and N-substituted glycine ethyl esters, on the other hand, is hardly affected by the size or structure of the parent thiol or amine, with all of these reactions proceeding in high yield. MTO-catalyzed cycloaddition reactions occur between EDA and aromatic imines, olefins, and carbonyl compounds. Three-membered ring products are formed: aziridines, cyclopropanes, and epoxides, respectively. The reactions favor the formation of trans products, and provide a convenient route for the preparation of aziridines. Intermediate carbenoid and nitrenoid species have been proposed. In the presence of an oxygen source such as an epoxide, ethyl diazoacetate and azibenzil are converted to an oxalic acid monoethyl ester and tobenzil; at the same time the epoxide was converted to an olefin. These results provide further support for the proposed intermediate, a cyclic species containing Re, O, and CHCO2Et (or, occasionally, CPhC(O)Ph)in a three-membered ring.
- Zhu, Zuolin,Espenson, James H.
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p. 9901 - 9907
(2007/10/03)
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- Metallkomplexe mit biologisch wichtigen Liganden LXI. Addition von α-Aminosaeureestern an koordinierte Olefine von + und (1,5-Hexadien)PtCl2
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Glycine ethylester is added to the coordinated olefin of + to give the complexes +BF4- (1).The reaction of α-amino acid esters with (1,5-hexadiene)PtCl2 affords the compound
- Zahn, Ingo,Polborn, Kurt,Beck, Wolfgang
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p. 397 - 405
(2007/10/02)
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