- Structure–activity relationships and docking studies of hydroxychavicol and its analogs as xanthine oxidase inhibitors
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Hydroxychavicol (HC), which is obtained from the leaves of Piper betle LINN. (Piperaceae), inhibits xanthine oxidase (XO) with an IC50 value of 16.7μM, making it more potent than the clinically used allopurinol (IC50=30.7μM). Herein, a structure–activity relationship analysis of the polar part analogs of HC was conducted and an inhibitor was discovered with a potency 13 times that of HC. Kinetic studies have revealed that HC and its active analog inhibit XO in an uncompetitive manner. The binding structure prediction of these inhibitor molecules to the XO complex with xanthine suggested that both compounds (HC and its analog) could simultaneously form hydrogen bonds with xanthine and XO.
- Nishiwaki, Keiji,Ohigashi, Kanae,Deguchi, Takahiro,Murata, Kazuya,Nakamura, Shinya,Matsuda, Hideaki,Nakanishi, Isao
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p. 741 - 747
(2018/07/05)
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- Cross-Coupling Reactions of Aryldiazonium Salts with Allylsilanes under Merged Gold/Visible-Light Photoredox Catalysis
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A method for the cross-coupling reactions of aryldiazonium salts with trialkylallylsilanes via merged gold/photoredox catalysis is described. The reaction is proposed to proceed through a photoredox-promoted generation of an electrophilic arylgold(III) intermediate that undergoes transmetalation with allyltrimethylsilane to form allylarenes.
- Akram, Manjur O.,Mali, Pramod S.,Patil, Nitin T.
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supporting information
p. 3075 - 3078
(2017/06/23)
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- Hydroquinone-Based Biarylic Polyphenols as Redox Organocatalysts for Dioxygen Reduction: Dramatic Effect of Orcinol Substituent on the Catalytic Activity
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A series of 18 new biaryls has been synthesized and investigated with regard to their organocatalytic efficiency. They consist of a hydroquinone core linked to a phenol or a resorcinol moiety. It is shown that the resorcinol moiety substituted on its meta position has a strong impact on the catalytic activities of these compounds towards the reduction of dioxygen by diethylhydroxylamine (DEHA) in aqueous medium. While the derivative consisting of the two cores spaced by three methylene units is completely inactive, substitution on the hydroquinone part leads to tremendously active catalysts, especially the biaryl consisting of methoxyhydroquinone-orcinol. Two mechanisms are proposed to explain the dramatic efficiency of the novel hydroquinone-based biarylic polyphenols for the catalytic reduction of dioxygen, both considering the influence of the orcinol moiety on the semiquinone anion intermediate. As a first hypothesis, this substituent could promote its direct reduction by DEHA to regenerate the hydroquinone, which will react again to regenerate the semiquinone. On the other hand, an intramolecular hydrogen bond could enhance the reactivity of the semiquinone anion toward dioxygen by an addition–elimination mechanism. In this case, the elimination would provide the corresponding quinone but, since the reduction of the quinones by DEHA is much slower than the observed kinetics, a reduction by DEHA prior to the elimination has to be considered to generate the semiquinone anion instead of the quinone. (Figure presented.).
- Lebeuf, Rapha?l,Nardello-Rataj, Véronique,Aubry, Jean-Marie
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p. 268 - 278
(2017/02/05)
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- 2-Prenylated m-dimethoxybenzenes as potent inhibitors of 15-lipo-oxygenase: inhibitory mechanism and SAR studies
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15-lipo-oxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance of enzymes has led to the development of mechanistic studies, product analysis, and synthesis of inhibitors. In this study, a series of allyl and prenyl dimethoxybenzenes were synthesized and their inhibitory potency against soybean 15-Lipo-oxygenase (L1; EC 1,13,11,12) was determined. Among the synthetic compounds, 2,6-dimethoxy-1-isopentenyl-4-methylbenzene, 2,6-dimethoxy-1-geranyl-4-methylbenzene, and 2,6-dimethoxy-1-farnesyl-4-methylbenzene showed the most potent inhibitory activity with IC50 values of 7.6, 5.3, and 0.52?μm, respectively. For some of the compounds, SAR studies showed acceptable relationship between inhibitory potency and enzyme–ligand interactions. Radical scavenging assessment results apart from the SAR studies indicate that electronic properties are the major factors for lipo-oxygenase inhibition potency of the mentioned compounds. Based on the theoretical studies, it was suggested that CH…O intramolecular hydrogen bond between ortho-methoxy oxygen and methine hydrogen atoms is one of the major factors in the stability of 2,6-dimethoxyallyl(or prenyl)benzenes radical via the planarity fixation between phenyl and allyl (or prenyl) pi orbitals.
- Jabbari, Atena,Sadeghian, Hamid,Salimi, Alireza,Mousavian, Mina,Seyedi, Seyed M.,Bakavoli, Mehdi
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p. 460 - 469
(2016/10/19)
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- Cascade multicomponent synthesis of indoles, pyrazoles, and pyridazinones by functionalization of alkenes
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The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivative
- Matcha, Kiran,Antonchick, Andrey P.
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supporting information
p. 11960 - 11964
(2015/01/09)
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- Deprotonative metalation of aromatic compounds by using an amino-based lithium cuprate
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Deprotonative cupration of aromatic compounds by using amino-based lithium cuprates was optimized with 2,4-dimethoxypyrimidine and 2-methoxypyridine as the substrates and benzoyl chloride as the electrophile. [(tmp)2CuLi] (+2 LiCl) (tmp=2,2,6,6-tetramethylpiperidino) was identified as the best reagent and its use was extended to anisole, 1,4-dimethoxybenzene, other substituted pyridines, furan, thiophene and derivatives, and N-Boc-indole (Boc=tert-butyloxycarbonyl). Of the electrophiles employed to attempt the interception of the generated aryl cuprates, aroyl chlorides, iodomethane, and diphenyl disulfide efficiently reacted. In addition, different oxidative agents were identified to afford symmetrical biaryls. Finally, palladium-catalyzed coupling with aryl halides was optimized and allowed the synthesis of different aryl derivatives in medium to good yields.
- Nguyen, Tan Tai,Marquise, Nada,Chevallier, Floris,Mongin, Florence
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experimental part
p. 10405 - 10416
(2011/10/12)
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- Synthesis and SAR comparative studies of 2-allyl-4-methoxy-1-alkoxybenzenes as 15-lipoxygenase inhibitors
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A group of 2-alkoxy-5-methoxyallylbenzene were designed, synthesised and evaluated as potential inhibitors of the soybean 15-lipoxygenase (SLO) on the basis of the eugenol and esteragol structures. Compound 4d showed the best half maximal inhibitory concentration (IC50) for SLO inhibition (IC 50=5.9±0.6 μM). All the compounds were docked in the SLO active site retrieved from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB entry: 1IK3) and showed that the allyl group of the synthetic compounds similar to the linoleic acid double bond, were oriented toward the Fe3+-OH moiety in the active site of the enzyme and this conformation was especially fixed by the hydrophobic interaction of the 2-alkoxy group with Leu515, Trp519, Val 566 and Ile572. It was concluded that the molecular volume and shape of the alkoxy moiety was a major factor in the inhibitory potency variation of the synthetic compounds.
- Sadeghian, Hamid,Seyedi, Seyed Mohammad,Attaran, Neda,Jabbari, Atena,Jafari, Zeinab
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p. 238 - 244
(2011/11/12)
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- Dialkoxybenzene and dialkoxyallylbenzene feeding and oviposition deterrents against the cabbage looper, trichoplusia ni: Potential insect behavior control agents
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The antifeedant, oviposition deterrent, and toxic effects of individual dialkoxybenzene compounds/sets and of hydroxy- or alkoxy-substituted allylbenzenes, obtained through Claisen rearrangement of substituted allyloxybenzenes, were assessed against the cabbage looper, Trichoplusia ni, in laboratory bioassays. Most of the compounds/sets strongly deterred larval feeding, with some exhibiting mild toxic and oviposition deterrent effects as well. Some of the compounds/sets were more active than the commercial insect repellent, DEET (N,N-diethyl-m-toluamide), as both feeding and oviposition deterrents against the cabbage looper. On the basis of the obtained oviposition data a general hypothesis was proposed regarding the oviposition sites: one binding mode with the alkyl and allyl groups on the same side of the benzene ring resulted in deterrence, the other with alkyl and allyl groups on opposite sides of the benzene ring resulted in stimulation. The results suggest some structure-activity relationships useful in improving the efficacy of the compounds and designing new, nontoxic insect control agents for agriculture.
- Akhtar, Yasmin,Yu, Yang,Isman, Murray B.,Plettner, Erika
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p. 4983 - 4991
(2011/08/06)
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- Deprotonative metalation of substituted aromatics using mixed lithium-cobalt combinations
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The deprotonation of anisole was attempted using different homo- and heteroleptic TMP/Bu mixed lithium-cobalt combinations. Using iodine to intercept the metalated anisole, an optimization of the reaction conditions showed that in THF at room temperature 2 equiv of base were required to suppress the formation of the corresponding 2,2′-dimer. The origin of the dimer was not identified, but its formation was favored with allyl bromide as electrophile. The metalated anisole was efficiently trapped using iodine, anisaldehyde, and chlorodiphenylphosphine, and moderately employing benzophenone, and benzoyl chloride. 1,2-, 1,3-, and 1,4-dimethoxybenzene were similarly converted regioselectively to the corresponding iodides. It was observed that 2-methoxy- and 2,6-dimethoxypyridine were more prone to dimerization than the corresponding benzenes when treated similarly. Involving ethyl benzoate in the metalation-iodination sequence showed that the method was not suitable to functionalize substrates bearing reactive functions.
- Dayaker, Gandrath,Chevallier, Floris,Gros, Philippe C.,Mongin, Florence
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experimental part
p. 8904 - 8910
(2011/01/04)
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- METHODS AND COMPOSITIONS FOR CONTROL OF CABBAGE LOOPER, Trichoplusia ni
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The invention provides in part dialkoxybenzene compounds for controlling infestation by a Trichoplusia ni, and methods thereof. The compounds include a compound of Formula I: where R1 may be methyl, ethyl, propyl, n-butyl, isopentyl(3-methylbutyl) or allyl; R2 may be at positions 2, 3 or 4 and may be H, methyl, ethyl, propyl, n-butyl, isopentyl(3-methylbutyl) or allyl; and R3 may be optionally present at positions 2, 3 and 4, and is allyl; except that when R2 is at position 2, R3 if present is at position 3, and when R2 is at position 3, R3 if present is at positions 2 or 4, and when R2 is at position 4, R3 if present is at position 2, and when R2 is at position 4 and R3, if present, has reacted with an OH group at position 1 in a Markovnikov sense, then R3 becomes R4, a dihydrofuran.
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Page/Page column 23
(2010/07/04)
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- New Gilman-type lithium cuprate from a copper(II) salt: synthesis and deprotonative cupration of aromatics
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Deprotonative cupration of aromatics including heterocycles (anisole, 1,4-dimethoxybenzene, thiophene, furan, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, and 2,4-dimethoxypyrimidine) was realized in tetrahydrofuran at room temperature using the Gilman-type amido-cuprate (TMP)2CuLi in situ prepared from CuCl2·TMEDA through successive addition of 1 equiv of butyllithium and 2 equiv of LiTMP. The intermediate lithium (hetero)arylcuprates were evidenced by trapping with iodine, allyl bromide, methyl iodide, and benzoyl chlorides, the latter giving the best results. Symmetrical dimers were also prepared from lithium azine and diazine cuprates using nitrobenzene as an oxidative agent.
- Nguyen, Tan Tai,Chevallier, Floris,Jouikov, Viatcheslav,Mongin, Florence
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experimental part
p. 6787 - 6790
(2010/04/29)
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- Electrophilic allylation of arenes with in situ generated allyltriarylbismuthonium compound: The Bismuth-mediated polarity inversion of allylsilanes
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Reaction of triarylbismuth difluorides 1 with allyltrimethylsilane 2 in CH2Cl2 in the presence of BF3·OEt2 at low temperature generates allyltriarylbismuthonium compound 3 as a pale yellow solution, in which aromatic hydrocarbons and ethers, triphenylphosphine, dimethyl sulfide, p-toluenesulfinate, and thiophenol are all readily allylated to afford the corresponding allyl derivatives in moderate to good yields.
- Matano, Yoshihiro,Yoshimune, Masanori,Suzuki, Hitomi
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p. 7475 - 7478
(2007/10/02)
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- STRUCTURE-ACTIVITY RELATIONSHIPS OF PHENYLPROPANOIDS AS GROWTH INHIBITORS OF THE GREEN ALGA SELENASTRUM CAPRICORNUTUM
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Twenty-seven commercial or synthetic phenylpropanoids have been tested in broth against the unicellular alga Selenastrum capricornutum.The antialgal activity seems to be linked to the number as well as to the position of the methoxyl group in the molecule.A slight effect of the side chain substitution was also observed. Key Word Index - Selenastrum capricornutum; allelochemicals; phenylpropanoids.
- Greca, Marina Della,Monaco, Pietro,Pollio, Antonino,Previtera, Lucio
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p. 4119 - 4124
(2007/10/02)
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- SYNTHESIS OF ERBSTATIN
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A simple and convenient synthesis of the tyrosinespecific protein kinase inhibitor, erbstatin (1) from cheap and easily accessible 4-methoxyphenol is described.
- Deshmukh, M. N.,Joshi, Shreerang V.
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p. 1483 - 1490
(2007/10/02)
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- Selective Demethylative Cyclisation of 2-Methoxy-allylbenzenes
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Treatment of 3-substituted 2-methoxyallylbenzenes with dry HBr in CHCl3 causes selective demethylative cyclisation to give 7-substituted 2-methyl-2,3-dihydrobenzofurans.The reaction involves mutual participation of allyl and 2-methoxyl groups and is sterically accelerated by substituents vicinal to OCH3.The reaction does not take place in high dielectric solvents such as DMF or DMSO.A propable mechanism envisaging a non-classical ionic transition state is proposed and the synthetic utility of this reaction is also demonstrated.
- Devakumar, C.,Mukerjee, S. K.
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p. 368 - 372
(2007/10/02)
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- Iodine(III)-Mediated Allylaton of Aromatic Compounds and Alcohols Using Allylmetal (Group IVb) Compounds
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The reaction of allylmetal (group IVb) compounds with aromatic compounds and iodosylbenzene in the presence of BF3-Et2O afforded the corresponding allylation products.Allylation of alcohols was also carried out to give allyl ethers.The activation of iodosylbenzene by the coordination of BF3-Et2O was assumed to be one of the most important factors for the reaction.The involvement of the reactive allyliodine(III) compounds in these reactions is discussed.Keywords - hypervalent organoiodine compound, iodosylbenzene; allylsilane; allylgermane; allylstannane; allyliodine(III) compound
- Ochiai, Masahito,Fujita, Eiichi,Arimoto, Masao,Yamaguchi, Hideo
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- Umpolung of Reactivity of Allylsilane, Allylgermane, and Allylstannane: Allylation of Aromatic Compounds with Allylmetal and Allylthallium Bis(trifluoroacetate)
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A direct allylation of aromatic compounds using allylsilane, allylgermane, or allylstannane (1) and arylthallium bis(trifluoroacetate) has been developed.The actual transmetalation reagent for 1 in the reaction was proposed to be thallium (III) trifluoroacetate (2), which was proposed together with diarylthallium trifluoroacetate by the disproportionation of arylthallium bis(trifluoroacetate).Keywords-allylation of aromatic compound; allylsilane; allylgermane; allylstannane; arylthallium bis(trifluoroacetate)
- Ochiai, Masahito,Fujita, Eiichi,Arimoto, Masao,Yamaguchi, Hideo
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p. 3994 - 3999
(2007/10/02)
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- UMPOLUNG OF REACTIVITY OF ALLYLSILANE, ALLYLGERMANE, AND ALLYLSTANNANE VIA THEIR REACTION WITH THALLIUM (III) SALT: A NEW ALLYLATION REACTION FOR AROMATIC COMPOUND
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A new direct allylation of the aromatic compound has been developed.A combination of allylsilane, allylgermane, or allylstannane and thallium (III) trifluoroacetate gave rise to an allyl cationic species which was allowed to react with an aromatic compound, a nucleophile, to give allylation product(s) in good yields.
- Ochiai, Masahito,Arimoto, Masao,Fujita, Eiichi
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p. 4491 - 4494
(2007/10/02)
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- Organocopper Chemistry of Quinone Bisketals. Application to the Synthaais of Isoprenoid Quinone Systems
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The reactions of organocuprates of 1,4-benzoquinone and 1,4-naphthoquinone bisketals are reported.These reagents, formed from the corresponding lithium reagent, cuprous iodide, and dimethyl sulfide react efficiently with allylic bromides (allyl, prenyl, geranyl, and phytyl), often with utilization of greater than one R group of the R2CuLi.Their reactions with acid chlorides and benzyl bromide proceed with acceptable efficiency, but they are unreactive toward a number of other substrates.The utility of this chemistry in the synthesis of menaquinone-2, phylloquinone,cymopol, and cymopol methyl ether is described.
- Chenard, Bertrand L.,Manning, Michael J.,Raynolds, Peter W.,Swenton, John S.
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p. 378 - 384
(2007/10/02)
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