- Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium
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Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.
- Xu-Xu, Qing-Feng,Nishii, Yuji,Uetake, Yuta,Sakurai, Hidehiro,Miura, Masahiro
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p. 17952 - 17959
(2021/11/16)
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- Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study
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A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC50= 1–12 μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range.
- W?glarz-Tomczak, Ewelina,Burda-Grabowska, Ma?gorzata,Giurg, Miros?aw,Mucha, Artur
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p. 5254 - 5259
(2016/11/09)
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- Crucial role of selenium in the virucidal activity of benzisoselenazol- 3(2h)-ones and related diselenides
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Various N-substituted benzisoselenazol-3(2H)-ones and their non-seleniumcontaining analogues have been synthesized and tested against selected viruses (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in antiviral activity. The data presented here show that the presence of selenium is crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their isostructural analogues having different groups but lacking selenium either did not show any antiviral activity or their activity was substantially lower. The open-chain analogues of benzisoselenazol- 3(2H)-ones-diselenides also exhibited high antiviral activity while selenides and disulfides were completely inactive towards model viruses.
- Pietka-Ottlik, Magdalena,Potaczek, Piotr,Piasecki, Egbert,Mlochowski, Jacek
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p. 8214 - 8228
(2011/03/19)
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- Cu-catalyzed efficient synthetic methodology for ebselen and related se-N heterocycles
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An efficient copper-catalyzed method for the synthesis of biologically important ebselen and related analogues containing a Se-N bond has been developed. This is the first report of a catalytic process of selenation and Se-N bond formation reaction. Copper-catalyzed reaction tolerates functional groups such as amides, hydroxyls, ethers, nitro, fluorides, and chlorides. The best results are obtained by using a combination of potassium carbonate as a base, iodo- or bromo-arylamide substrates, selenium powder, and copper iodide catalyst.
- Balkrishna, Shah Jaimin,Bhakuni, Bhagat Singh,Chopra, Deepak,Kumar, Sangit
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supporting information; experimental part
p. 5394 - 5397
(2011/02/26)
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- Diselenobis-benzoic acid amides of primary and secondary amines and processes for the treatment of diseases in humans caused by a cell injury
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The present invention relates to new diselenobis-benzoic acid amides of primary and secondary amines of the general formula (I): STR1 and processes for the treatment of diseases in humans caused by a cell injury.
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- MECHANISM OF THE CATALYTIC REDUCTION OF HYDROPEROXIDES BY EBSELEN : A SELENIUM - 77 NMR STUDY
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Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one 1, a non-toxic selenium containing heterocyclic compound has been shown to display both anti-inflammatory activity in vivo and GSH-Px-like activity in vitro.Using (1)H and (77)Se NMr we investigated the mechanism of reduction of hydroperoxides by thiols in the presence of 1.A catalytic cycle depending on the formation of diselenides and selenylsulfides was found.The selenic acid oxidation level present in compound 1 is particularly stable because of the intermolecular cyclisation.This contracts with previously reported results concerning the oxidation of organoselenium compounds.
- Fisher, Hartmut,Dereu, Norbert
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p. 757 - 768
(2007/10/02)
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