- Discovery of pyrrolidine-2,3-diones as novel inhibitors of p. Aeruginosa pbp3
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The alarming threat of the spread of multidrug resistant bacteria currently leaves clinicians with very limited options to combat infections, especially those from Gram-negative bacteria. Hence, innovative strategies to deliver the next generation of antibacterials are urgently needed. Penicillin binding proteins (PBPs) are proven targets inhibited by β-lactam antibiotics. To discover novel, non-β-lactam inhibitors against PBP3 of Pseudomonas aeruginosa, we optimised a fluorescence assay based on a well-known thioester artificial substrate and performed a target screening using a focused protease-targeted library of 2455 compounds, which led to the identification of pyrrolidine-2,3-dione as a potential scaffold to inhibit the PBP3 target. Further chemical optimisation using a one-pot three-component reaction protocol delivered compounds with excellent target inhibition, initial antibacterial activities against P. aeruginosa and no apparent cytotoxicity. Our investigation revealed the key structural features; for instance, 3-hydroxyl group (R2) and a heteroaryl group (R1) appended to the N-pyrroldine-2,3-dione via methylene linker required for target inhibition. Overall, the discovery of the pyrrolidine-2,3-dione class of inhibitors of PBP3 brings opportunities to target multidrug-resistant bacterial strains and calls for further optimisation to improve antibacterial activity against P. aeruginosa.
- López-Pérez, Arancha,Freischem, Stefan,Grimm, Immanuel,Weiergr?ber, Oliver,Dingley, Andrew J.,López-Alberca, María Pascual,Waldmann, Herbert,Vollmer, Waldemar,Kumar, Kamal,Vuong, Cuong
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- Synergistic Nanostructured MnOx/TiO2 Catalyst for Highly Selective Synthesis of Aromatic Imines
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This work reports the development of a synergistic nanostructured MnOx/TiO2 catalyst, with highly dispersed MnOx nanoparticles (4.5±1 nm) on shape-controlled TiO2 nanotubes (8–11 nm width and 120–280 nm length), for selective synthesis of valuable aromatic imines at industrially important conditions. Pristine TiO2 nanotubes exhibited 97 % imine selectivity at a 38.3 % benzylamine conversion, whereas very low imine selectivity was obtained over commercial TiO2 materials, indicating the catalytic significance of shape-controlled TiO2 nanotubes. The MnOx nanoparticle/TiO2 nanotube (10 wt% Mn) catalyst calcined at 400 °C showed the best activity with 95.6 % benzylamine conversion and 99.9 % imine selectivity. This catalyst exhibited good recyclability for four times and is effective for converting numerous benzylamines into higher yields of imines. The high catalytic performance of MnOx/TiO2 nanotubes was attributed to higher number of redox sites (Mn3+), high dispersion of Mn species, and shape-controlled structure of TiO2, indicating that this catalyst could be a promising candidate for selective oxidation reactions.
- Sudarsanam, Putla,K?ckritz, Angela,Atia, Hanan,Amin, Mohamad Hassan,Brückner, Angelika
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p. 1990 - 1997
(2021/02/27)
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- One-pot multicomponent reaction of catechols, ammonium acetate, and aldehydes for the synthesis of benzoxazole derivatives using the fe(iii)-salen complex
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The Fe(III)-salen complex has been applied successfully as a catalyst for the novel, simple, efficient, and one-pot multicomponent synthesis of benzoxazole derivatives from catechols, ammonium acetate as the nitrogen source, and aldehydes (nontoxic and cheap alternatives of amines) for the first time. Using this procedure, a wide range of benzoxazoles was successfully synthesized in the presence of a catalyst in EtOH under mild conditions, and all products were obtained in excellent yields. To the best of our knowledge, this method is the first example of the multicomponent synthesis of benzoxazole derivatives using these starting materials. The notable features such as the use of air that is considered as a benign oxidant and EtOH as a green solvent, ease of product separation, readily available and inexpensive aldehydes, and mild conditions make our procedure more efficient and practical for organic synthesis. Moreover, the current protocol is successfully applied to synthesize desirable products on a large scale.
- Sharghi, Hashem,Aboonajmi, Jasem,Aberi, Mahdi
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p. 6567 - 6577
(2020/06/08)
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- Enantioselective Reductive Coupling of Imines Templated by Chiral Diboron
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We herein report a general, practical, and highly efficient method for asymmetric synthesis of a wide range of chiral vicinal diamines via reductive coupling of imines templated by chiral diboron. The protocol features high enantioselectivity and stereospecificity, mild reaction conditions, simple operating procedures, use of readily available starting materials, and a broad substrate scope. The method signifies the generality of diboron-enabled [3,3]-sigmatropic rearrangement.
- Chen, Dongping,Li, Kaidi,Tang, Wenjun,Xu, Guangqing,Xu, Ronghua,Zhou, Mingkang
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supporting information
p. 10337 - 10342
(2020/07/04)
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- Kinetic Resolution of Secondary Allyl Boronates and Their Application in the Synthesis of Homoallylic Amines
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Highly enantioenriched, chromatographically-stable secondary allyl boronates featuring a 1,1,2,2-tetraethyl-1,2-ethanediol fragment (Epin) were obtained by kinetic resolution of their racemic mixtures. The Epin group at boron considerably improved stability of allyl boronates allowing them to be readily isolated by chromatography on silica. The resolved reagents were applied in stereoselective synthesis of homoallylic amines with an internal double bond employing unprotected imines formed in situ from aldehydes and ammonia. The reactions proceeded with an excellent transfer of chirality.
- Villar, Laura,Orlov, Nikolai V.,Kondratyev, Nikolay S.,Uria, Uxue,Vicario, Jose L.,Malkov, Andrei V.
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supporting information
p. 16262 - 16265
(2018/10/20)
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- Structural characteristics and catalytic performance of nanostructured Mn-doped CeO2 solid solutions towards oxidation of benzylamine by molecular O2
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This work reports a thorough investigation of nanosized Mn-doped ceria (Ce0.7Mn0.3O2-δ, CM) as an efficient catalyst for oxidation of benzylamine under solvent-free conditions. These catalysts were prepared by a coprecipitation method followed by calcination at 773 and 1073?K. Effect of Mn doping was examined by a variety of characterization techniques. XRD results confirmed formation of single-phase Ce-O-Mn solid solution, and TEM studies showed nanosized nature of particles. BET surface area of CeO2 was significantly enhanced after Mn incorporation. Raman, XPS and H2-TPR results revealed that Mn cations in ceria lattice increase concentration of structural oxygen vacancies and reducibility of ceria. Among various catalysts, the CM calcined at 773?K exhibited a high conversion (~71%), product selectivity (~99.8%), and excellent stability. The better performance has been proved to be due to synergetic interaction between Ce and Mn ions thereby enhanced surface area, improved reducibility, and increased surface adsorbed oxygen species.
- Rangaswamy, Agolu,Venkataswamy, Perala,Devaiah, Damma,Ramana, Singuru,Reddy, Benjaram M.
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p. 136 - 147
(2017/01/03)
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- Synthesis, photophysical and acidochromic properties of a series of tetrahydrodibenzo[a,i]phenanthridine chromophores
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A series of luminescent 5-aryl-tetrahydrodibenzo[a,i]phenanthridines was developed through modified synthetic protocol using SnCl2-acetic acid as a catalyst. The synthesis was consistent with various functionalities and significantly improves t
- Balijapalli, Umamahesh,Udayadasan, Sathiskumar,Shanmugam, Easwaramoorthi,Kulathu Iyer, Sathiyanarayanan
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p. 233 - 244
(2016/05/24)
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- Metal-free, one-pot oxidative conversion of aldehydes to primary thioamides in aqueous media
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One-pot tandem reactions of a variety of aldehydes with aqueous ammonia, molecular iodine, and O,O-diethyl dithiophosphoric acid readily afford the corresponding primary thioamides. This is an inexpensive, practical, and metal-free way of accessing various thioamides from aldehydes in aqueous media. The pure products are obtained simply by filtration followed by successive washing with aqueous sodium thiosulfate and water. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Yadav, Arvind K.,Srivastava, Vishnu P.,Yadav, Lal Dhar S.
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supporting information
p. 408 - 416
(2014/01/06)
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- Photocatalytic aerobic oxidation of amines to imines on BiVO4 under visible light irradiation
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BiVO4 was found to be an efficient photocatalyst under visible light irradiation for selective oxidation of amines to imines with high activity (99% conversion) and selectivity (up to 99%) using oxygen as an oxidant.
- Yuan, Bo,Chong, Ruifeng,Zhang, Bao,Li, Jun,Liu, Yan,Li, Can
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supporting information
p. 15593 - 15596
(2015/01/08)
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- A highly efficient and useful synthetic protocol for the synthesis of bis[aryl(diethoxyphosphoryl)methyl]amines from aromatic aldehydes using acetyl chloride as an efficient catalyst
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A highly efficient and useful method for the synthesis of bis[aryl(diethoxyphosphoryl)methyl]amines has been developed. The treatment of aromatic aldehydes with ammonia followed by reaction with diethyl phosphite in the presence of acetyl chloride as cata
- Kaboudin, Babak,Jafari, Ehsan
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p. 1823 - 1826
(2008/02/12)
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- Correlation analysis of reactivity in the oxidation of substituted benzylamines by pyridinium hydrobromide perbromide
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The oxidation of benzylamine and twenty-seven ortho-, meta- and para-substituted benzylamines by pyridinium hydrobromide perbromide (PHPB), in dimethylsulphoxide (DMSO), leads to the formation of the corresponding aldimines. The reactions are of first order with respect to both PHPB and the amine. The oxidation of deuterated benzylamine exhibited a substantial kinetic isotope effect (kII/kD = 3.20 at 303 K). An addition of pyridinium bromide does not affect the rate. PHPB itself has been postulated as the reactive oxidizing species. The rates of the oxidation of para- and meta-substituted benzylamines were correlated with Taft's and Swain's field and resonance substituent constants. The oxidation of para-substituted benzylamines showed an excellent correlation with Taft's σI and σRBA values; the meta-compounds correlated best with σI and σR0 values. Rates of the ortho-substituted compounds showed a significant correlation with Charton's triparametric equation. Suitable mechanism has been proposed.
- Garg, Dimple,Goyal, Archana,Kothari, Seema
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p. 935 - 941
(2007/10/03)
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- Kinetics and mechanism of the oxidation of substituted benzylamines by oxo(salen)manganese(V) complexes
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The oxidation of substituted benzylamines by substituted oxo(salen)manganese(V) complexes, in acetonitrile, leads to the formation of the corresponding aldimines. The reaction is first order with each of the amine and the Mn(V) complex. The oxidation of [1,1-2H2]benzylamine exhibited the presence of substantial kinetic isotope effects. The rates of oxidation of 19 amines by 4 Mn(V) complexes have been determined. Correlation analyses of the rates of oxidation of the 19 monosubstituted benzylamines were performed with various single and multiparametric equations. The rates of the oxidation showed excellent correlations in terms of Yukawa-Tsuno and Brown's equations. The polar reaction constants are negative. The rate of reduction of the substituted Mn(V) complexes showed an excellent correlation in terms of the Hammett equation with positive reaction constants. The reactivity-selectivity principle (RSP) is obeyed in this reaction. The validity of RSP was verified by Exner's mathematical procedure. Suitable mechanisms have been discussed.
- Dubey, Rashmi,Kotai, Laszlo,Banerji, Kalyan K.
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p. 218 - 235
(2007/10/03)
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- Kinetics and mechanism of the oxidation of substituted benzylamines by hexamethylenetetramine-bromine
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The oxidation of substituted benzylamines by hexamethylenetetramine-bromine (HABR) to the corresponding aldimines is first order with respect to each the amine and HABR. It is proposed that HABR itself is the reactive oxidizing species. The oxidation of deuterated benzylamine (PhCD2NH2) indicated a substantial kinetic isotope effect (kH/kD = 5.60 at 293 K). This confirmed the cleavage of an α-C-H bond in the rate-determining step. Correlation analyses of the rates of oxidation of 20 monosubstituted benzylamines were performed with various single-and multi-parametric equations. The rates of the oxidation showed excellent correlations in terms of the Yukawa-Tsuno and Brown equations. The polar reaction constants were negative. The oxidation exhibited extensive cross-conjugation, in the transition state, between the electron-donating substituents and the reaction centre. A mechanism involving a hydride ion transfer from the amine to HABR, in the rate-determining step, is proposed. Copyright
- Dubey, Rashmi,Kothari, Seema,Banerji, Kalyan K.
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p. 103 - 107
(2007/10/03)
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- Correlation analysis of reactivity in the oxidation of substituted benzylamines by benzyltrimethylammonium tribromide
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The oxidation of benzylamine and twenty-seven ortho-, meta- and para-monosubstituted benzylamines by benzyltrimethylammonium tribromide (BTMAB), in dimethylsulphoxide (DMSO), leads to the formation of corresponding aldimines. The reaction is first order with respect to both BTMAB and the amine. The oxidation of deuterated benzylamine exhibited a substantial kinetic isotope effect. Addition of benzyltrimethylammonium bromide does not affect the rate. Tribromide ion has been postulated as the reactive oxidizing species. The rates of the oxidation of para- and meta-substituted benzylamines showed excellent correlation in terms of both Taft's dual substituent-parameter and Charton's triparametric LDR equations, whereas the ortho-substituted compounds exhibited the best correlation with the Charton's tetraparametric LDRS equation. The oxidation of para-substituted benzylamines is more susceptible to the delocalization effect than is the oxidation of ortho- and meta-substituted compounds, which display a greater dependence on the field effect. The low positive value of the η suggests the presence of an electron-deficient centre in the rate-determining transition state with less charge separation. A suitable mechanism has been proposed.
- Sankhla, Rekha,Kothari, Seema
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p. 541 - 546
(2007/10/03)
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