- Lithium aluminum amides: New reagents for the synthesis of imines
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Aldehydes (4 eqiv.) react under mild conditions with LiAL(NHR1)4 (1 eqiv.) to give the corresponding imines in 90% yield and no polymerization was observed upon reaction of aliphatic aldehyde 3.
- Solladie-Cavallo,Bencheqroun,Bonne
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Read Online
- Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands
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A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-D-xylulose-5-phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+-chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6–16.4 μM against Plasmodium falciparum parasites and IC50 values of 5.2 – 10.2 μM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
- Adeyemi, Christiana M.,Hoppe, Heinrich C.,Isaacs, Michelle,Mnkandhla, Dumisani,Lobb, Kevin A.,Klein, Rosalyn,Kaye, Perry T.
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- Design, synthesis and biological evaluation of imidazole and oxazole fragments as HIV-1 integrase-LEDGF/p75 disruptors and inhibitors of microbial pathogens
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We describe here the synthesis of libraries of novel 1-subtituted-5-aryl-1H-imidazole, 5-aryl-4-tosyl-4,5-dihydro-1,3-oxazole and 5-aryl-1,3-oxazole fragments via microwave (MW)-assisted cycloaddition of para-toluenesulfonylmethyl isocyanide (TosMIC) to imines and aldehydes. The compounds obtained were biologically evaluated in an AlphaScreen HIV-1 IN-LEDGF/p75 inhibition assay with six imidazole-based compounds (16c, 16f, 17c, 17f, 20a and 20d) displaying more than 50% inhibition at 10 μM, with IC50 values ranging from 7.0 to 30.4 μM. Additionally the hypothesis model developed predicts all active scaffolds except 20d to occupy similar areas as the N-heterocyclic (A) moiety and two aromatic rings (B and C) of previously identified inhibitor 5. These results indicate that the identified compounds represent a viable starting point for their use as templates in the design of next generation inhibitors targeting the HIV-1 IN and LEDGF/p75 protein-protein interaction. In addition, the in vitro antimicrobial properties of these fragments were tested by minimum inhibitory concentration (MIC) assays showing that compound 16f exhibited a MIC value of 15.6 μg/ml against S. aureus, while 17f displayed a similar MIC value against B. cereus, suggesting that these compounds could be further developed to specifically target those microbial pathogens.
- Rashamuse, Thompho J.,Harrison, Angela T.,Mosebi, Salerwe,van Vuuren, Sandy,Coyanis, E. Mabel,Bode, Moira L.
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- Substituted 4-Oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic esters by a tandem imine addition-SNAr reaction
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A tandem imine addition-SNAr annulation reaction has been developed as a new approach to the synthesis of 4-oxo-1,2,3,4- tetrahydroquinoline-3-carboxylic esters. A series of these structures has been generated by reacting selected imines with tert-butyl 2-fluoro-5- nitrobenzoylacetate. Structural variations in the final products are accomplished by changing the substituents on the imine and the alkyl group of the ester. The title compounds are isolated as their enols in 55-97% yield without the need for added base or catalysts. The synthesis of the starting materials as well as mechanistic studies and further synthetic conversions of the products are presented.
- Bunce, Richard A.,Schammerhorn, James E.,Sigle, Jessica
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p. 373 - 380
(2013/06/04)
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- Ugi four-component reaction of alcohols: Stoichiometric and catalytic oxidation/MCR sequences
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A new, simple, and efficient procedure for the one-pot Ugi four-component reaction of alcohols instead of aldehydes is described. Using a stoichiometric amount of IBX or only 1-2% of sodium 2-iodobenzenesulfonate in the presence of Oxone, a wide range of primary alcohols were oxidized to the aldehyde that were directly engaged in the Ugi four-component reaction to afford α-acetamidoamides in good to excellent yields.
- Drouet, Fleur,Masson, Géraldine,Zhu, Jieping
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supporting information
p. 2854 - 2857
(2013/07/26)
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- Palladium-catalyzed aryl iodide carbonylation as a route to imidazoline synthesis: Design of a five-component coupling reaction
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Take five: A new method employing aryl halide carbonylation to directly access heterocycles has been described (see scheme). In a single palladium-catalyzed reaction the catalyst mediates two consecutive carbonylation steps, thereby converting five components (aryl iodide, two units imine, and two units CO) into an imidazoline ring.
- Bontemps, Sebastien,Quesnel, Jeffrey S.,Worrall, Kraig,Arndtsen, Bruce A.
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supporting information; body text
p. 8948 - 8951
(2011/10/19)
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- A highly diastereoselective synthesis of α-hydroxy-β-amino acid derivatives via a Lewis acid catalyzed three-component condensation reaction
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A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection was investigated through a computational model of the key reaction step.
- Gassa, Federico,Contini, Alessandro,Fontana, Gabriele,Pellegrino, Sara,Gelmi, Maria Luisa
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experimental part
p. 7099 - 7106
(2010/12/24)
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- Sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation Protocol for the synthesis of indenoisoquinolines
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Copper-catalyzed coupling of imines, vinylstannanes, or alkynes and o-bromoaroyl chlorides followed by Pd(0)-catalyzed annulations afforded indenoisoquinolines. Protocols requiring minimal purifications were developed, providing new methods for the construction of combinatorial libraries.
- Jayanth, Thiruvellore Thatai,Zhang, Lei,Johnson, Thomas S.,Malinakova, Helena C.
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supporting information; experimental part
p. 815 - 818
(2009/07/18)
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- Eco-friendly synthesis of imines by ultrasound irradiation
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A series of imines was synthesized by an ultrasound-assisted reaction of aldehydes and primary amines using silica as the promoter. Products were obtained in high yields even in large scale synthesis.
- Guzen, Karla P.,Guarezemini, Alexandre S.,órf?o, Aline T.G.,Cella, Rodrigo,Pereira, Claudio M.P.,Stefani, Hélio A.
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p. 1845 - 1848
(2008/02/05)
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- Scandium triflate catalyzed cycloaddition of imines with 1,1-cyclopropanediesters: Efficient and diastereoselective synthesis of multisubstituted pyrrolidines
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A tandem ring-opening-cyclization reaction of cyclopropanes with imines in the presence of 5 mol% of scandium triflate was developed for the highly diastereoselective synthesis of multisubstituted pyrrolidines. The Royal Society of Chemistry 2006.
- Kang, Yan-Biao,Tang, Yong,Sun, Xiu-Li
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p. 299 - 301
(2007/10/03)
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- Efficient microwave-assisted solvent-free synthesis of N-substituted aldimines
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Neat non-volatile amines react with various aromatic aldehydes in the absence of any catalyst, solid support, or solvent, to give imines after a reaction time of eight minutes under microwave irradiation by a clean and very efficient process (yields: 75-100%). In the case of volatile amine, methylamine, 1,3-dimethylurea dispersed on montmorillonite K10 is used as an amine precursor to prepare the corresponding imines. Georg Thieme Verlag Stuttgart.
- Paquin, Ludovic,Hamelin, Jack,Texier-Boullet, Francoise
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p. 1652 - 1656
(2007/10/03)
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- Molecular sieves in ionic liquids as an efficient and recyclable medium for the synthesis of imines
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A great variety of imines were efficiently isolated in high yields from the reaction of aldehydes and amines in ionic liquids. The ionic liquids could be recovered and reused for at least five cycles without loss in the yields being a useful alternative to dichloromethane or diethyl ether, which are the commonly used solvents for this reaction.
- Andrade, Carlos Kleber Z.,Takada, Sayuri Cristina S.,Magalh?es Alves, Luana,Petrocchi Rodrigues, Juliana,Suarez, Paulo Anselmo Z.,Brand?o, Rodrigo Fleury,Soares, Valério Cassiano D.
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p. 2135 - 2138
(2007/10/03)
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- Preparation of benzolactams by Pd(OAC)2-catalyzed direct aromatic carbonylation
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We developed a new method for Pd(II)-catalyzed direct aromatic carbonylation in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air. The carbonylation proceeded with ortho-palladation, inducing a remarkable site selectivity to afford a variety of five- or six-membered benzolactams from secondary ω-arylalkylamines, such as N-alkylbenzylamines or N-alkylphenethylamines. Copyright
- Orito, Kazuhiko,Horibata, Akiyoshi,Nakamura, Takatoshi,Ushito, Harumi,Nagasaki, Hideo,Yuguchi, Motoki,Yamashita, Satoshi,Tokuda, Masao
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p. 14342 - 14343
(2007/10/03)
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- Synthesis of cytotoxic indenoisoquinoline topoisomerase I poisons
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A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6- ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo- 11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3- dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top i inhibitors were 6- (3-carboxy-1-propyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2,3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2- c]isoquinolinium Chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8,9-(methylenedioxy)- 5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4- hydroxybut-1-yl)-2-3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2- c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 clearable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1.
- Strumberg, Dirk,Pommier, Yves,Paull, Kenneth,Jayaraman, Muthusamy,Nagafuji, Pamela,Cushman, Mark
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p. 446 - 457
(2007/10/03)
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- Combinatorial synthesis of dihydropyridone libraries and their derivatives
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Polymer-supported quench methodology has been used for parallel purification of combinatorial libraries of dihydropyridones and their derivatives. The dihydropyridone scaffold was assembled via a solution phase Lewis acid catalyzed, hetero-Diels-Alder reaction. Further modifications allow for the rapid generation of subsequent aminopiperidine and acylaminopiperidine libraries utilizing a library from library approach.
- Creswell, Mark W.,Bolton, Gary L.,Hodges, John C.,Meppen, Malte
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p. 3983 - 3998
(2007/10/03)
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- Synthesis of 7,12-dihydro-12-phenyl-5H-6,12-methanodibenz[cf]azocines via N,N-dibenzylphenacylamines
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N,N-DibenzyIphenacylamines (1) were prepared in high yields by a onepot reaction and cyclized at room temperature to give 7,12-dihydro-12-phenyl-5H-6,12-methanodibenz[cf]azocines in high yields. 95% H2SO4 or 70% HClO4 was used as cyclization catalysts. The double-cyclization proceeds smoothly in the cases where electron-donating groups are present in both benzene ring. N-2,3-dimethoxybenzyl-N-benzylphenacylamine (If) gave the corresponding N-benzyl-1,2-dihydro-4-phenylisoquinoline on treatment with 95% H2SO4 while N-3,4-Dimethoxybenzyl-N-benzylphenacylamine (1a) at the same reaction conditions and reaction time cyclized to the corresponding dibenzazocine. However la gave the corresponding dihydroisoquinoline which disproportionates to give N-benzyl-1,2,3,4-tetrahydro-4-phenylisoquinoline and N-benzyl-4-phenylisoquinolinium when treated with 70% perchloric acid at room temperature.
- Coskun, Necdet,Bueyuekuysal, Levent
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