19643-45-9Relevant academic research and scientific papers
Catalytic oxidation of 2,4,6-tribromophenol using iron(III) complexes with imidazole, pyrazole, triazine and pyridine ligands
Igarashi, Mami,Zhu, Qianqian,Sasaki, Masahide,Kodama, Ritsu,Oda, Kohki,Fukushima, Masami
, p. 100 - 106 (2016)
Five types of non-heme iron complexes, coordinated with imidazole, pyrazole, triazine and pyridine ligands, which had been previously synthesized, were used in the following studies. Among these complexes, the mer-[FeCl3(terpy)] complex showed the highest catalytic activity for the oxidative degradation of 2,4,6-tribromophenol (TrBP) using KHSO5 as an oxygen donor. The turnover numbers for the degradation and debromination of TrBP in the mer-[FeCl3(terpy)]/KHSO5 catalytic system were estimated to be 1890 ± 1 and 4020 ± 216, respectively. The catalytic activity was significantly inhibited at pH 4-7 in the presence of a humic acid, a major component of landfill leachates. However, the percent of TrBP degradation and debromination increased at pH 8. GC/MS analyses showed that a major oxidation product was 2,6-dibromo-p-benoquinone (DBQ) and its level decreased with increasing reaction time, suggesting that organic acids (identified by LC/TOF-MS) are formed via the ring-cleavage of DBQ. Mineralization to CO2 was observed to be 15% as a result of the oxidation for a 3 h period, where TOC values before and after the reaction were measured. Absorption spectra of mer-[FeCl3(terpy)] with m-chloroperoxybenzoic acids as an oxygen donor in acetonitrile showed that a center metal, Fe, formed a peroxide complex with the oxygen donor.
Conversion of Human Neuroglobin into a Multifunctional Peroxidase by Rational Design
Chen, Shun-Fa,Liu, Xi-Chun,Xu, Jia-Kun,Li, Lianzhi,Lang, Jia-Jia,Wen, Ge-Bo,Lin, Ying-Wu
, p. 2839 - 2845 (2021)
Protein design has received much attention in the last decades. With an additional disulfide bond to enhance the protein stability, human A15C neuroglobin (Ngb) is an ideal protein scaffold for heme enzyme design. In this study, we rationally converted A15C Ngb into a multifunctional peroxidase by replacing the heme axial His64 with an Asp residue, where Asp64 and the native Lys67 at the heme distal site were proposed to act as an acid-base catalytic couple for H2O2 activation. Kinetic studies showed that the catalytic efficiency of A15C/H64D Ngb was much higher (～50-80-fold) than that of native dehaloperoxidase, which even exceeds (～3-fold) that of the most efficient native horseradish peroxidase. Moreover, the dye-decolorizing peroxidase activity was also comparable to that of some native enzymes. Electron paramagnetic resonance, molecular docking, and isothermal titration calorimetry studies provided valuable information for the substrate-protein interactions. Therefore, this study presents the rational design of an efficient multifunctional peroxidase based on Ngb with potential applications such as in bioremediation for environmental sustainability.
Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2-Symmetric Biaryls
Coombs, Gavin,Sak, Marcus H.,Miller, Scott J.
supporting information, p. 2875 - 2880 (2020/01/24)
We have demonstrated that small, modular, tetrameric peptides featuring the Lewis-basic residue β-dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester-bearing quinones to yield non-C2-symmetric BINOL-type scaffolds with good yields and enantioselectivity. The study culminates in the asymmetric synthesis of backbone-substituted scaffolds similar to 3,3′-disubstituted BINOLs, such as (R)-TRIP, with good (94:6 e.r.) to excellent (>99.9:0.1 e.r.) enantioselectivity after recrystallization, and a diastereoselective net arylation of the minimally modified nonsteroidal anti-inflammatory drug (NSAID) naproxen.
Unusual Chemistry in an Uncatalyzed Bromate-Aniline Oscillator: Ring-Contraction Oxidation of Aniline with Pulsative CO2 Production
Valent, Ivan,Pribus, Marek,Novák, Filip,Plánková, Sylvia,Bla?ko, Jaroslav,Kubinec, Róbert,Almássy, Ambroz,Filo, Juraj,Sigmundová, Ivica,Sebechlebská, Táňa,Lawson, Thuy Bich,Noszticzius, Zoltán
, p. 9669 - 9681 (2019/11/14)
The bromate-aniline oscillatory reaction was discovered 4 decades ago, but neither the detailed mechanism nor the key products or intermediates of the reaction were described. We report herein a detailed study of this reaction, which yielded new insights. We found that oscillatory oxidation of aniline by acidic bromate proceeds, to a significant extent, via a novel reaction pathway with the periodic release of carbon dioxide. Several products were isolated, and their structures, not described so far, were justified on the basis of MS and NMR. One of the main products of the reaction associated with the CO2 release route can be assigned to 2,2-dibromo-5-(phenylimino)cyclopent-3-en-1-one. A number of known compounds produced in the studied reaction, including unexpected brominated 1-phenylpyrroles and 1-phenylmaleimides, were identified by comparison with standards. A mechanism is suggested to explain the appearance of the detected compounds, based on coupling of the anilino radical with the produced 1,4-benzoquinone. We assume that the radical adduct reacts with bromine to form a cyclopropanone intermediate that undergoes a Favorskii-type rearrangement. Further oxidation and bromination steps including decarboxylation lead to the found brominated phenyliminocyclopentenones. The detected derivatives of 1-phenylpyrrole could be produced by a one-electron oxidation of a proposed intermediate 2-phenylamino-5-bromocyclopenta-1,3-dien-1-ol followed by β-scission with the abstraction of carbon monoxide. Such a mechanism is known from the combustion chemistry of cyclopentadiene. The proposed mechanism of this reaction provides a framework for understanding the observed oscillatory kinetics.
Halogen-Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules
Ungati, Harinarayana,Govindaraj, Vijayakumar,Nair, Chithra R.,Mugesh, Govindasamy
, p. 3391 - 3399 (2019/02/13)
The poor uptake of fluorescent probes and therapeutics by mammalian cells is a major concern in biological applications ranging from fluorescence imaging to drug delivery in living cells. Although gaseous molecules such as oxygen and carbon dioxide, hydrophobic substances such as benzene, and small polar but uncharged molecules such as water and ethanol can cross the cell plasma membrane by simple passive diffusion, many synthetic as well as biological molecules require specific membrane transporters and channel proteins that control the traffic of these molecules into and out of the cell. This work reports that the introduction of halogen atoms into a series of fluorescent molecules remarkably enhances their cellular uptake, and that their transport can be increased to more than 95 % by introducing two iodine atoms at appropriate positions. The nature of the fluorophore does not play a major role in the cellular uptake when iodine atoms are present in the molecules, as compounds bearing naphthalimide, coumarin, BODIPY, and pyrene moieties show similar uptakes. Interestingly, the introduction of a maleimide-based fluorophore bearing two hydroxyethylthio moieties allows the molecules to cross the plasma and nuclear membranes, and the presence of iodine atoms further enhances the transport across both membranes. Overall, this study provides a general strategy for enhancing the uptake of organic molecules by mammalian cells.
Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B
Feng, Yu,Liu, Jun,Carrasco, Yazmin P.,MacMillan, John B.,De Brabander, Jef K.
supporting information, p. 7130 - 7142 (2016/07/06)
We describe the isolation, structure elucidation, and total synthesis of the novel marine natural product rifsaliniketal and the total synthesis of the structurally related variants salinisporamycin and saliniketals A and B. Rifsaliniketal was previously proposed, but not observed, as a diverted metabolite from a biosynthetic precursor to rifamycin S. Decarboxylation of rifamycin provides salinisporamycin, which upon truncation with loss of the naphthoquinone ring leads to saliniketals. Our synthetic strategy hinged upon a Pt(II)-catalyzed cycloisomerization of an alkynediol to set the dioxabicyclo[3.2.1]octane ring system and a fragmentation of an intermediate dihydropyranone to forge a stereochemically defined (E,Z)-dienamide unit. Multiple routes were explored to assemble fragments with high stereocontrol, an exercise that provided additional insights into acyclic stereocontrol during stereochemically complex fragment-assembly processes. The resulting 11-14 step synthesis of saliniketals then enabled us to explore strategies for the synthesis and coupling of highly substituted naphthoquinones or the corresponding naphthalene fragments. Whereas direct coupling with naphthoquinone fragments proved unsuccessful, both amidation and C-N bond formation tactics with the more electron-rich naphthalene congeners provided an efficient means to complete the first total synthesis of rifsaliniketal and salinisporamycin.
Novel bioactivation pathway of benzbromarone mediated by cytochrome P450
Kitagawara, Yumina,Ohe, Tomoyuki,Tachibana, Kumiko,Takahashi, Kyoko,Nakamura, Shigeo,Mashino, Tadahiko
supporting information, p. 1303 - 1306 (2015/09/07)
Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl) benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity.
Synthesis of indolequinones from bromoquinones and enamines mediated by Cu(OAc)2H2O
Inman, Martyn,Moody, Christopher J.
supporting information; experimental part, p. 6023 - 6026 (2010/11/20)
A Cu(II)-mediated synthesis of indolequinones from the corresponding bromoquinones and enamines is reported. The key oxidative cyclization proceeds in good yield for a broad range of substrates and can be performed on a multigram scale, allowing access to biologically interesting structures.
Addition of silyloxydienes to 2,6-dibromo-1,4-benzoquinone: An approach to highly oxygenated bromonaphthoquinones for the synthesis of thysanone
Barker, David,Brimble, Margaret A.,Do, Peter,Turner, Peter
, p. 2441 - 2449 (2007/10/03)
The synthesis of tetraoxygenated bromonaphthoquinones 6a, 6b, 6c, 6d, key intermediates for a synthesis of the 3C protease inhibitor, thysanone, were investigated. Addition of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene 8 to 2,6-dibromo-1,4-benzoquinone 10 in benzene afforded a mixture of naphthoquinone 6a, arising from Diels-Alder addition followed by aromatisation, and Michael adduct 12. The Michael adduct 12 predominated when THF was used as solvent whereas 6a predominated when benzene was used. Naphthoquinone 6a underwent benzylation to naphthoquinone 6c. Addition of 1,1-dimethoxy-3-trimethylsilyloxy-1,3-butadiene 9 to 2,6-dibromo-1,4-benzoquinone 10 followed by benzylation failed to afford the desired bromonaphthoquinone 6d yet methylation did afford naphthoquinone 6b. Bromonaphthoquinone 6d was finally prepared from naphthol 18, obtained from addition of diene 9 to 1,4-benzoquinone 17, followed by ortho-bromination and oxidation. Attempted Sakurai allylation of bromonaphthoquinone 6d afforded naphthodihydrofuran 21. A similar observation was observed for 2-carbomethoxy-1,4-naphthoquinone 22 that also underwent Sakurai allylation to afford naphthodihydrofuran 23. The structure of Michael adduct 12 was confirmed by X-ray crystallography.
Rapid conversion of phenols to p-benzoquinones under acidic conditions with lead dioxide
Omura, Kanji
, p. 1145 - 1148 (2007/10/03)
Treatment of 4-unsubstituted and 4-halogenated phenols with PbO2 and 70% HClO4 in AcOH afforded the corresponding p-benzoquinones in fair to high yields. The oxidation of 4-substituted 2,6-di-tertbutylphenols 6 with PbO2 and 70% HClO4 in acetone gave 2,6-di-tert-butyl-p-benzoquinone (2).
