- Reduction of Aldehydes with Formic acid in Ethanol using Immobilized Iridium Nanoparticles on a Triazine-phosphanimine Polymeric Organic Support
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A novel triazine-phosphanimine polymeric organic support (TPA) was synthesized successfully by a controllable one-pot method using melamine (1,3,5-triazine-2,4,6-triamine) and trichlorophosphane (PCl3). The TPA substrate is a material incorporating P and N atoms which can coordinate with metals as a pincer ligand to stabilize them, providing an efficient heterogeneous support to prepare recyclable transition metal catalyst systems. In this study, TPA was used as support to immobilize iridium nanoparticles in the range of ~8 nm on its surface, resulting in the generation of a novel iridium nanocatalyst system (INP-TPA-POP). This catalyst system was characterized using different microscopic and spectroscopic techniques such as FT-IR, TEM, XPS, XRD, SEM, EDX, elemental analysis, ICP and BET analysis. The INP-TPA-POP nanocatalyst exhibited remarkable activity in reduction of aldehydes to alcohols using formic acids as reducing agent in ethanol as solvent.
- Panahi, Farhad,Haghighi, Fatemeh,Khalafi-Nezhad, Ali
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- Chemoselective transfer hydrogenation of aromatic and heterocyclic aldehydes by green chemically prepared cobalt oxide nanoparticles
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A new surfactant (quercetin) assisted hydrothermal method is used for the preparation of phase pure cobalt oxide (Co3O4) nanoparticles (Nps). The quercetin acted well as surfactant in producing size controlled Nps. The produced Nps were extensively characterized by various techniques to reveal its chemical composition, structure, morphology, size and thermal behavior. The main objective of the study is to employ the prepared material as heterogeneous catalyst for hydrogenation of therapeutically important aldehydes. The capability of the catalyst is appear to be good, since the yield of alcohols from structurally different aldehydes is adequate with short period of time. Also the catalyst is recyclable, stable, no need of addition of ligands for activation and environmentally benign.
- Krishnaveni,Lakshmi,Kaveri,Kadirvelu
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- Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors
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A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.
- Zhang,Xu,Wang,Kang
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p. 3006 - 3016
(2018/02/21)
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- Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis
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An unprecedented tandem N-alkylation-ionic aza-Cope (or Claisen) rearrangement-hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N-alkylation and subsequent microwave-irradiated ionic aza-Cope rearrangement-hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2-reverse quaternary-centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza-Cope rearrangement reaction proceeds highly regioselectively to give the quaternary-centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3-methylene-2,3-dihydro-1Hindole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2-reverse prenylated indoles, such as indolines, indolefused sultams and lactams, and the natural product bruceolline D.
- Chen, Xiaobei,Fan, Huaqiang,Zhang, Shilei,Yu, Chenguang,Wang, Wei
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supporting information
p. 716 - 723
(2016/01/12)
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- Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators
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Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3?nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.
- Greig, Iain R.,Baillie, Gemma L.,Abdelrahman, Mostafa,Trembleau, Laurent,Ross, Ruth A.
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p. 4403 - 4407
(2016/08/25)
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- Nanostructured RuO2 on MWCNTs: Efficient catalyst for transfer hydrogenation of carbonyl compounds and aerial oxidation of alcohols
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Multiwall carbon nanotubes (MWCNTs)/ruthenium dioxide nanoparticles (RuO2NPs) composite was prepared by a straightforward 'dry synthesis' method. After being well characterized, the prepared composite was used as a nanocatalyst (RuO2/MWCNT) for the transfer hydrogenation of carbonyl compounds. The excellent adhesion of RuO2NPs on the anchoring sites of MWCNTs was confirmed by TEM and Raman analyses. The weight percentage (7.97 wt%) and the chemical state (+4) of Ru in RuO2/MWCNT was confirmed by EDS and XPS analyses, respectively. It was found that the RuO2/MWCNT has a higher specific surface area of 189.3 m2 g-1. Initially the reaction conditions were optimized and then the scope of the catalytic system was extended with a wide range of carbonyl compounds. The influence of the size of RuO2NPs on the transfer hydrogenation of carbonyl compounds was also studied. The RuO2/MWCNT is highly chemoselective, heterogeneous in nature, reusable and highly stable. Owing to the high stability of the used catalyst (u-RuO2/MWCNT), it was further calcinated at high temperature to obtain RuO2 nanorods (NRs) hybrid MWCNTs. Then the hybrid material was used as a catalyst (r-RuO 2/MWCNT) for the aerial oxidation of alcohols and the result was found to be good.
- Gopiraman,Babu, S. Ganesh,Karvembu,Kim
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- Selective transformations of carbonyl functions in the presence of α,β-unsaturated ketones: Concise asymmetric total synthesis of decytospolides A and B
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Enones selectively react with a combination of PPh3 and TMSOTf to produce phosphonium silyl enol ethers, which work as protective groups of enones during the reduction of other carbonyl functions and can be easily deprotected to regenerate parent enones at workup. Furthermore, the first ketone selective alkylations in the presence of enones were also accomplished. This in situ protection method was applied to concise asymmetric total syntheses of decytospolides A and B.
- Yahata, Kenzo,Minami, Masaki,Watanabe, Kei,Fujioka, Hiromichi
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supporting information
p. 3680 - 3683
(2014/08/05)
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- Towards a facile and convenient synthesis of highly functionalized indole derivatives based on multi-component reactions
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A library of potentially bioactive compounds through the novel 1H-indole-methyl-isocyanide and MCRs has been described. A flexible and efficient synthesis affording great complexity and diversity is achieved with moderate to good yields with no need for protection and deprotection steps. This journal is The Royal Society of Chemistry 2014.
- Neochoritis, Constantinos G.,Doemling, Alexander
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supporting information
p. 1649 - 1651
(2014/03/21)
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- The cruciferous phytoalexins rapalexin A, brussalexin A and erucalexin: Chemistry and metabolism in Leptosphaeria maculans
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The interactions of the cruciferous phytoalexins rapalexin A (1), brussalexin A (2) and erucalexin (3) with the fungal plant pathogen Leptosphaeria maculans were analyzed and their inhibitory activities against this pathogen were determined. The reaction of L. maculans to N-methyl S-(indolyl-3-methyl)carbamodithioate, an analogue of brussalexin A, was also investigated. Rapalexin A was resistant to metabolism and was the most inhibitory of all compounds tested, suggesting that increasing concentrations of rapalexin A in Brassica species would improve their disease resistance to L. maculans. By contrast, erucalexin was quickly detoxified by reduction to yield 3-dihydroerucalexins. The relative configurations of the diastereomeric mixture of dihydroerucalexins were established by 1D 1H nuclear Overhauser enhancement spectroscopy (NOE). Brussalexin A was chemically unstable decomposing mainly to indolyl-3-methanol, a product with anti-cancer properties. For this reason, brussalexin A might be of interest to use as a prodrug.
- Pedras, M. Soledade C.,Sarma-Mamillapalle, Vijay K.
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p. 3991 - 3996
(2012/09/22)
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- A novel oxidative transformation of alcohols to nitriles: An efficient utility of azides as a nitrogen source
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An efficient methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been developed. This methodology employs DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H 2O.
- Rokade, Balaji V.,Malekar, Sanjeev K.,Prabhu, Kandikere Ramaiah
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supporting information; body text
p. 5506 - 5508
(2012/07/03)
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- Cytochrome P450BM-3 reduces aldehydes to alcohols through a direct hydride transfer
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Cytochrome P450BM-3 catalyzed the reduction of lipophilic aldehydes to alcohols efficiently. A kcat of ~25min-1 was obtained for the reduction of methoxy benzaldehyde with wild type P450BM-3 protein which was higher than in the isolated reductase domain (BMR) alone and increased in specific P450-domain variants. The reduction was caused by a direct hydride transfer from preferentially R-NADP2H to the carbonyl moiety of the substrate. Weak substrate-P450-binding of the aldehyde, turnover with the reductase domain alone, a deuterium incorporation in the product from NADP2H but not D2O, and no inhibition by imidazole suggests the reductase domain of P450BM-3 as the potential catalytic site. However, increased aldehyde reduction by P450 domain variants (P450BM-3 F87A T268A) may involve allosteric or redox mechanistic interactions between heme and reductase domains. This is a novel reduction of aldehydes by P450BM-3 involving a direct hydride transfer and could have implications for the metabolism of endogenous substrates or xenobiotics.
- Kaspera, Rüdiger,Sahele, Tariku,Lakatos, Kyle,Totah, Rheem A.
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experimental part
p. 464 - 468
(2012/07/27)
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- Mild synthetic approach to novel indole-1-carbinols and preliminary evaluation of their cytotoxicity in hepatocarcinoma cells
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A mild and versatile method for the synthesis of some novel indole-1-carbinols has been developed via one-pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO 2. The solvent-free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole-1-carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.
- Zedda, Gloria,Simbula, Gabriella,Begala, Michela,Pibiri, Monica,Floris, Costantino,Casu, Mariano,Casu, Laura,Tocco, Graziella
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experimental part
p. 195 - 202
(2012/06/04)
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- Composition for Topical Use
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The use, as a dermatological or cosmetic medicament, of compounds capable of transiently interacting with the AhR receptor (aryl hydrocarbon receptor) as agents for modulating skin functions such as sebaceous function, skin healing, skin atrophy termed “dermatoporosis”, estrogen deprivation and defense against infection, without inducing other toxic effects of the TCDD type. The compounds that interact with the AhR receptor are chosen in that they have a metabolism favorable to the dissociation of these effects, in particular by virtue of in situ production from a precursor and/or metabolization modulated in situ.
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- Efficient synthesis of brussalexin A, a remarkable phytoalexin from Brussels sprouts
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The synthesis of brussalexin A, the first phytoalexin containing an allyl thiolcarbamate group, and its selective inhibitory activity against fungal plant pathogens is described. The Royal Society of Chemistry.
- Pedras, M. Soledade C.,Zheng, Qing-An,Sarwar, Mohammed G.
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p. 1167 - 1169
(2008/02/03)
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- Reactivity toward thiols and cytotoxicity of 3-methylene-2-oxindoles, cytotoxins from indole-3-acetic acids, on activation by peroxidases
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Oxidation of indole-3-acetic acid and its derivatives by peroxidases such as that from horseradish produces many products, including 3-methylene-2-oxindoles. These have long been associated with biological activity, but their reactivity has not been characterized. We have previously demonstrated the potential value of substituted indole acetic acids and horseradish peroxidase as the basis for targeted cancer therapy, since the compounds are of low cytotoxicity until oxidized, when high cytotoxicity is observed; the combination of prodrug and enzyme depletes intracellular thiols. In this study, 3-methylene-2-oxindole and derivatives substituted in the 4-, 5-, or 6-position with methyl, F, or Cl have been synthesized and their reactivity toward representative thiol nucleophiles (glutathione, cysteine, and a cysteinyl peptide) measured using stopped-flow kinetic spectrophotometry. Rate constants were in the range ~2 × 103 to 2 × 104 M-1 s-1 at pH 7.4, 25°C, implying a lifetime of a few tens of milliseconds for these methylene oxindoles in the cellular environment and diffusion distances of a few micrometers. As expected, halogen substitution decreased the rate of production of the methylene oxindoles on treatment of horseradish peroxidase. The cytotoxicities of the compounds were measured using Chinese hamster V79 fibroblast-like cells in vitro. The halogen-substituted derivatives were much more cytotoxic than the 5-methyl analogue or the parent (unsubstituted) compound, consistent with the trends in rate constant for reaction with the thiols. The results show that the cytotoxic response in the prodrug (indole acetic acid) and enzyme (horseradish peroxidase) system reflects the reactivity of methylene oxindoles toward nucleophiles much more than the rate of generation of the oxindoles, and helps explain the possible advantages of 5-fluoroindole-3 -acetic acid compared to IAA as a lead compound for investigation in targeted cancer therapy.
- Folkes, Lisa K.,Rossiter, Sharon,Wardman, Peter
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p. 877 - 882
(2007/10/03)
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- Aerobic oxidation of indole-3-acetic acid catalysed by anionic and cationic peanut peroxidase
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The catalytic properties of anionic and cationic peanut peroxidases with regards to the oxidation of indole-3-acetic acid (IAA) by molecular oxygen at low pH have been studied. Transient kinetic studies demonstrate that only cationic peroxidases (peanut and horseradish) but not anionic peroxidases (such as anionic tobacco and anionic peanut peroxidases) form a stable compound III in the course of IAA oxidation. The failure to observe inhibition in the presence of superoxide dismutase is consistent with the formation of compound III from a ternary complex comprising ferric enzyme, IAA and dioxygen at the initiation step. Product analysis by HPLC showed an enhanced rate of IAA oxidation in the presence of superoxide dismutase. Co- addition of superoxide dismutase and catalase demonstrates that this stimulation is not due to the formation of hydrogen peroxide. The correlation between initial rates of IAA degradation and product accumulation indicates that skatole hydroperoxide is a primary reaction product and indole-3- methanol is the product of its subsequent enzymatic reduction. The relative catalytic activities for IAA oxidation by tobacco:horseradish isoenzyme c:anionic peanut:cationic peanut peroxidase are 28:20:2:1.
- Gazaryan, Irina G.,Chubar, Tatyana A.,Mareeva, Elena A.,Lagrimini, L. Mark,Van Huystee, Robert B.,Thorneley, Roger N.F.
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p. 175 - 186
(2007/10/03)
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- Synthesis and in vitro evaluation of 3-(1-Azolylmethyl)-1H-indoles and 3-(1-azoly1-1-phenylmethyl)-1H-indoles as inhibitors of P450 arom
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In the challenge to develop potent inhibitors of aromatase for reducing the levels of estrogens, we found that azolyl-substituted indoles inhibit aromatase activity. 3-(1-Azolylmethyl)-1H-indoles 9-15 and 3-(1-azolyl-1- phenylmethyl)-1H-indoles 22-25 were prepared, and tested on their ability to inhibit P450 arom. Analysis of the inhibitory effect exerted by several derivatives (11, 12, 22, and 23) on microsomal aromatase in vitro activity indicates that azolyl-substituted indoles containing an imidazole moiety are more potent inhibitors than triazole derivatives. In the first series, the introduction of the N-benzyl moiety has been found to enhance the inhibitory profile of these 3-(1-azolylmethyl)-1H-indole derivatives. The corresponding 4-fluoro derivative 12 displays the highest inhibitory activity (IC50 = 0.0718 μM) of all investigated compounds; thus, 12 is 258 times as potent as aminoglutethimide (AG). The presence of a chloro grouping in para position of the phenyl ring in compounds 22 and 24 exerts a positive effect only in the triazol-1-yl sub-series: compound 25 is 4-fold more potent than 24.
- Le Borgne, Marc,Marchand, Pascal,Duflos, Muriel,Delevoye-Seiller, Benedicte,Piessard-Robert, Sylvie,Le Baut, Guillaume,Hartmann, Rolf W.,Palzer
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p. 141 - 145
(2007/10/03)
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- Mechanistic studies on the cytochrome P450-catalyzed dehydrogenation of 3- methylindole
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The mechanism of 3-methyleneindolenine (3MEI) formation from 3- methylindole (3MI) in goat lung microsomes was examined using stable isotope techniques. 3MEI is highly electrophilic, and its production is a principal factor in the systemic pneumotoxicity of 3MI. Noncompetitive intermolecular isotope effects of (D)V = 3.3 and (D)(V/K) = 1.1 obtained after deuterium substitution at the 3-methyl position indicated either that hydrogen abstraction from the methyl group was not the initial rate-limiting step or that this step was rate-limiting and was masked by a high forward commitment and low reverse commitment to catalysis. An intramolecular isotope effect of 5.5 demonstrated that hydrogen atom abstraction was probably the initial oxidative and rate-limiting step of 3MI bioactivation or that deprotonation of an aminium cation radical, produced by one-electron oxidation of the indole nitrogen, was rate-limiting. However, a mechanism which requires deprotonation of the aminium cation radical is probably precluded by an unusual requirement for specific base catalysis at a site in the cytochrome P450 enzyme other than the heme iron. The pattern of 18O incorporation into indole-3-carbinol from 18O2 and H218O indicated that approximately 80% of the indole-3-carbinol was formed in goat lung microsomes by hydration of 3MEI. However, the inverse reaction, dehydration of indole-3-carbinol, did not significantly contribute to the formation of 3MEI. These results show that 3MEI was formed in a cytochrome P450-catalyzed dehydrogenation reaction in which the rate-limiting step was presumably hydrogen atom abstraction from the 3-methyl position. The ratio of the amounts of 3MEI to indole-3-carbinol formed (50:1) indicated that dehydrogenation of 3MI is an unusually facile process when compared to the dehydrogenation of other substrates catalyzed by cytochrome P450 enzymes.
- Skiles,Yost
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p. 291 - 297
(2007/10/03)
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- Calcium metal in liquid ammonia for selective reduction of organic compounds
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Selective reduction of functional groups by use of dissolving calcium metal was performed, and the results are in comparison with those by lithium and sodium metals. Reduction with 2.0-2.2 equiv of calcium led chromone (1) to 4-chromanone (2, 75% yield), coumarin (4) to dihydrocoumarin (5, 76% yield) and 3-(2-hydroxyphenyl)-1-propanol (6, 6% yield), α-tetralone (7) to 1,2,3,4-tetrahydro-1-naphthol (8, 81% yield), and β-methoxystyrene (12) to methyl phenethyl ether (13, 85% yield). Performance of reductions on the same substrates by use of 4.0 equiv of lithium or sodium metal gave over-reduced products. Reduction of indole-3-carboxaldehyde (15) to 3-indolemethanol (16), 1-acetylnaphthalene (17) to 1-acetyl-3,4-dihydronaphthalene (18), and trans-4-phenyl-3-buten-2-one (19) to 4-phenyl-2-butanone (20) were accomplished by use of calcium, lithium, and sodium metals, among which calcium gave the highest yields (80-90%). Being a milder reducing agent than lithium and sodium, calcium metal in liquid ammonia offered a better selectivity.
- Hwu, Jih Ru,Wein,Leu, Yi-Jing
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p. 1493 - 1498
(2007/10/03)
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- Free-Radical Intermediates and Stable Products in the Oxidation of Indole-3-acetic Acid
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The free-radical intermediates and the stable products formed on one-electron oxidation of indole-3-acetic acid (IAA) in aqueous solution were investigated.The dibromine radical anion generated radiolytically reacted with IAA to yield the IAA radical cation.In acid solution, the latter decays by a first-order process (k = 1.8E4 s-1) to yield carbon dioxide and the skatole radical.At pH 7 it deprotonates (pKa = 5.09 +/- 0.02), giving the indolyl radical, which decays only by a bimolecular process (rate constant of first-order reactions -1) which yields indole-3-carbinol as one of the products.Under steady-state irradiation at pH 7 the free radicals had a sufficient lifetime to allow the small fraction of radical cation present in equilibrium to undergo decarboxylation, consistent with the observed formation of carbon dioxide.Glutathione reacted with the indol radical, regenerating IAA, and with the skatole radical to yield skatole.In the presence of oxygen the skatole radical is rapidly converted to a peroxyl radical, which appears to decay only by bimolecular reactions with indole-3-aldehyde as one of the products.No evidence was found for the reaction of the peroxyl radical with glutathione or for elimination of superoxide.
- Candeias, Luis P.,Folkes, Lisa K.,Dennis, Madeleine F.,Patel, Kantilal B.,Everett, Steven A.,et al.
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p. 10131 - 10137
(2007/10/02)
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- A SYNTHESIS METHOD OF INDOLE-3-METHANAMINE AND/OR GRAMINE FROM INDOLE-3-CARBOXALDEHYDE, AND ITS APPLICATION FOR THE SYNTHESES OF BRASSININ, ITS 4-SUBSTITUTED ANALOGS, AND 1,3,4,5-TETRAHYDROPYRROLOQUINOLINE
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Simple conversion method of indole-3-carboxaldehyde into gramine and/or indole-3-methanamine was developed.The present method realized short step syntheses of brassinin, 4-iodo-, methoxy-, 4-methoxy, and 4-nitrobrassinin, 4-methoxyindole-3-acetonitrile, and 1,3,4,5-tetrahydropyrroloquinoline.
- Yamada, Fumio,Kobayashi, Kensuke,Shimizu, Aya,Aoki, Naokatsu,Somei, Masanori
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p. 2783 - 2804
(2007/10/02)
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- IDENTIFICATION OF 1-METHOXYINDOLYL-3-METHYL ISOTHIOCYANATE AS AN INDOLE GLUCOSINOLATE BREAKDOWN PRODUCT
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The putative indole glucosinolate enzymic hydrolysis product, 1-methoxyindolyl-3-methyl isothiocyanate has been detected for the first time using low and high resolution mass spectrometry.
- Hanley, A. Bryan,Parsley, Keith R.
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p. 769 - 771
(2007/10/02)
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- Chemistry of Indole Glucosinolates: Intermediacy of Indol-3-ylmethyl Isothiocyanates in the Enzymic Hydrolysis of Indole Glucosinolates
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The enzymic hydrolysis of 1-methoxyindol-3-ylmethyl glucosinolate (1b) proceeds via the corresponding isothiocyanate (2b), thus providing evidence for a previously unsubstantiated breakdown pathway and establishing a link with 1-methoxycyclobrassinin (4b) and related indole phytoalexins.
- Hanley, A. Bryan,Parsley, Keith R.,Lewis, Jenny A.,Fenwick, G. Roger
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p. 2273 - 2276
(2007/10/02)
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