- Reactions of benzyltriphenylphosphonium salts under photoredox catalysis
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The development of benzyltriphenylphosphonium salts as alkyl radical precursors using photoredox catalysis is described. Depending on substituents, the benzylic radicals may couple to form C-C bonds or abstract a hydrogen atom to form C-H bonds. A natural product, brittonin A, was also synthesized using this method.
- Boldt, Andrew M.,Dickinson, Sidney I.,Ramirez, Jonathan R.,Benz-Weeden, Anna M.,Wilson, David S.,Stevenson, Susan M.
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supporting information
p. 7810 - 7815
(2021/09/28)
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- Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
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A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
- Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
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- Cis alkenes stabilized by intramolecular sulphur?π interactions
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A series of alkenes with bistable isomers were obtained containing a thiophene/azoheteroaryl backbone. Visible light and heat-induced reversible cis ? trans isomerizations were evidenced by UV-Vis and 1H NMR spectra. The stabilization of cis alkenes was attributed to intramolecular sulphur?π (S?π) interactions, which were further supported by theoretical calculations.
- Zhao, Xiaolei,Zheng, Wei,Zhang, Yi,Huang, Wei
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supporting information
p. 814 - 817
(2020/01/29)
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- Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation
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Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 μM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.
- Liu, Hao,Chen, Li,Zhou, Fei,Zhang, Yun-Xiao,Xu, Ji,Xu, Meng,Bai, Su-Ping
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supporting information
p. 3089 - 3096
(2019/06/14)
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- Transition-Metal-Free Sulfuration/Annulation of Alkenes: Economical Access to Thiophenes Enabled by the Cleavage of Multiple C-H Bonds
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A novel, atom economical, and transition-metal-free strategy for the synthesis of thiophenes from substituted buta-1-enes with potassium sulfide has been presented. The reaction achieves double C-S bond formations via cleavage of multiple C-H bonds and provides an efficient approach to access various functionalized thiophenes. Moreover, the strategy can also be used for the synthesis of thiophenes from 1,4-diaryl-1,3-dienes. Mechanistically, DMSO plays a role of oxidant and S3?- in situ generated from K2S is involved.
- Chen, Liang,Min, Hao,Zeng, Weilan,Zhu, Xiaoming,Liang, Yun,Deng, Guobo,Yang, Yuan
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supporting information
p. 7392 - 7395
(2019/01/03)
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- Ionic Liquids as Solvents for SN2 Processes. Demonstration of the Complex Interplay of Interactions Resulting in the Observed Solvent Effects
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Bimolecular nucleophilic substitution reactions between triphenylphosphine and benzylic electrophiles have been examined in an ionic liquid to probe interactions with species along the reaction coordinate. Trends in the rate constant were found on both varying the leaving group and the electronic nature of the aromatic ring. In all the cases considered, interactions between the components of the ionic liquid and the transition state were shown to be more significant in determining reaction outcome than previously observed for this class of reaction. This demonstrates the importance of considering interactions of the ionic liquid components with all species along the reaction coordinate when investigating the origin of ionic liquid solvent effects, along with how such effects might be exploited.
- Schaffarczyk McHale, Karin S.,Haines, Ronald S.,Harper, Jason B.
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p. 1162 - 1168
(2019/01/04)
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- One-Step Synthesis of Substituted Benzofurans from ortho- Alkenylphenols via Palladium-Catalyzed C=H Functionalization
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A dehydrogenative oxygenation of C(sp2)=H bonds with intramolecular phenolic hydroxy groups has been developed, which provides a straightforward and concise access to structurally diversely benzofurans from ortho-alkenylphenols. The reaction is catalyzed by palladium on carbon (Pd/C) without any oxidants and sacrificing hydrogen acceptors.
- Yang, Dejun,Zhu, Yifei,Yang, Na,Jiang, Qiangqiang,Liu, Renhua
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supporting information
p. 1731 - 1735
(2016/06/09)
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- Synthesis and anti-inflammatory activity of phenylbutenoid dimer analogs
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Several phenylbutenoid dimer (PBD) analogs were synthesized and evaluated for their inhibitory activities against nitric oxide (NO) production and TNF-α release. The PBD analogs were synthesized via Diels - Alder and subsequent Schlosser reactions as key steps. Among the tested compounds, two analogs (8c, 8f) exhibited much stronger inhibitory activity against LPS-stimulated NO production and TNF-α release in RAW 264.7 cells than that of wogonin.
- Kim, Sung-Soo,Fang, Yuanying,Park, Haeil
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p. 1676 - 1680
(2015/07/15)
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- Development of a Phase-Transfer-Catalyzed, [2,3]-Wittig Rearrangement
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An investigation into the use of phase-transfer catalysis for the [2,3]-sigmatropic rearrangement of allyloxy carbonyl compounds is described. Initial studies focused on identifying viable substrate classes that would undergo selective [2,3]-rearrangement under phase-transfer catalysis. Under certain conditions, the [2,3]-sigmatropic rearrangement of allyloxy carbonyl compounds takes place in the presence of a phase-transfer agent, providing a rare example of a phase-transfer-catalyzed unimolecular reaction. In the course of this investigation, it was found that catalysis is dependent on several variables including base concentration, catalyst structure, and substrate lipophilicity. Preliminary testing of chiral, nonracemic phase-transfer catalysts has shown promising levels of enantioselectivity for future development.
- Denmark, Scott E.,Cullen, Lindsey R.
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p. 11818 - 11848
(2015/12/11)
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- Synthesis of 2-phenylnaphthalenes from styryl-2-methoxybenzenes
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A new simple and efficient method for the synthesis of 2-phenylnaphthalenes from electron-rich 1-styryl-2-methoxybenzenes has been described. The reaction proceeds via TFA catalyzed C-C bond cleavage followed by intermolecular [4+2]-Diels-Alder cycloaddition of an in situ formed styrenyl trifluoroacetate intermediate. The quantum chemical calculations identified the transition state for the cycloaddition reaction and helped in tracing the reaction mechanism. The method has been efficiently utilized for synthesis of the phenanthrene skeleton and a naphthalene-based potent and selective ER-β agonist. This journal is
- Mudududdla, Ramesh,Sharma, Rohit,Abbat, Sheenu,Bharatam, Prasad V.,Vishwakarma, Ram A.,Bharate, Sandip B.
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supporting information
p. 12076 - 12079
(2015/02/19)
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- Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity
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Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 & MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".
- Parihar, Swati,Kumar, Amit,Chaturvedi, Amit K.,Sachan, Naresh Kumar,Luqman, Suaib,Changkija, Bendangla,Manohar, Murli,Prakash, Om,Chanda,Khan, Feroz,Chanotiya,Shanker, Karuna,Dwivedi, Anila,Konwar, Rituraj,Negi, Arvind S.
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p. 332 - 344
(2013/11/19)
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- Z-selective copper-catalyzed asymmetric allylic alkylation with grignard reagents
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Allylic gem-dichlorides undergo regio- and enanantioselective (er up to 99:1) copper-catalyzed allylic alkylation with Grignard reagents affording chiral Z-vinyl chlorides. This highly versatile class of synthons can be subjected to Suzuki cross coupling affording optically active Z-alkenes and 1,3-cis,trans dienes.
- Giannerini, Massimo,Fananas-Mastral, Martin,Feringa, Ben L.
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supporting information; experimental part
p. 4108 - 4111
(2012/04/10)
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- Synthesis and structure-activity analysis of new phosphonium salts with potent activity against African trypanosomes
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A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were synthesized and tested in vitro against several wild type and resistant lines of Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO, and TbB48). More than half of the compounds tested showed a submicromolar EC50 against these parasites. The compounds did not display any cross-resistance to existing diamidine therapies, such as pentamidine. In most cases, the compounds displayed a good selectivity index versus human cell lines. None of the known T. b. brucei drug transporters were required for trypanocidal activity, although some of the bisphosphonium compounds inhibited the low affinity pentamidine transporter. It was found that phosphonium drugs act slowly to clear a trypanosome population but that only a short exposure time is needed for irreversible damage to the cells. A comparative molecular field analysis model (CoMFA) was generated to gain insights into the SAR of this class of compounds, identifying key features for trypanocidal activity.
- Taladriz, Andrea,Healy, Alan,Flores Pérez, Eddysson J.,Herrero García, Vanessa,Ríos Martínez, Carlos,Alkhaldi, Abdulsalam A. M.,Eze, Anthonius A.,Kaiser, Marcel,De Koning, Harry P.,Chana, Antonio,Dardonville, Christophe
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supporting information; experimental part
p. 2606 - 2622
(2012/06/01)
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- 1-[(E)-2-arylethenyl]-2,2-diphenylcyclopropanes: Kinetics and mechanism of rearrangement to cyclopentenes
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Kinetic measurements for the thermal rearrangement of 2,2-diphenyl-1-[(E)- styryl]cyclopropane (22a) to 3,4,4-triphenylcyclopent-1-ene (23a) in decalin furnished ΔHρm{{-{isom}^{ne }}}$=31.0±1.2kcal mol-1 and ΔSρm{{-{isom}^{ne }}}$=-6. 0±2.6e.u. The lowering of ΔHa‰ by 20kcal mol-1, compared with the rearrangement of the vinylcyclopropane parent, is ascribed to the stabilization of a transition structure (TS) with allylic diradical character. The racemization of (+)-(S)-22a proceeds with ΔHρm{{-{rac}^{ne }}}$=28.2±0.8kcal mol -1 and ΔSρm{{-{rac}^{ne }}}$=-5±2e.u., and is at 150° 106 times faster than the rearrangement. Seven further 1-(2-arylethenyl)-2,2-diphenylcyclopropanes 22, (E)- and (Z)-isomers, were synthesized and characterized. The (E)-compounds showed only modest substituent influence in their krac (at 119.4°) and kisom (at 159.3°) values. The lack of solvent dependence of rate opposes charge separation in the TS, but a linear relation of log krac with log p.r.f., i.e., partial rate factors of radical phenylations of ArH, agrees with a diradical TS. The ring-opening of the preponderant s-trans-conformation of 22 gives rise to the 1-exo-phenylallyl radical 26 that bears the diphenylethyl radical in 3-exo-position, and is responsible for racemization. The 1-exo-3-endo-substituted allylic diradical 27 arises from the minor s-gauche-conformation of 22 and is capable of closing the three- or the five-membered ring, 22 or 23, respectively. The discussion centers on the question whether the allylic diradical is an intermediate or merely a TS. Quantum-chemical calculations by Houk etal. (1997) for the parent vinylcyclopropane reveal the lack of an intermediate. Can the conjugation of the allylic diradical with three Ph groups carve the well of an intermediate? Copyright
- Mulzer, Johann,Huisgen, Rolf,Arion, Vladimir,Sustmann, Reiner
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experimental part
p. 1359 - 1388
(2011/10/09)
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- Studies toward the photochemical synthesis of functionalized [5]- and [6] carbohelicenes
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(Chemical Equation Presented) An efficient route to nonsymmetrical helical menthyl esters by means of an oxidative photocyclization reaction of dissymmetric bis-stilbenes is reported. The developed route allows the introduction of functionality on rings A, E, or F, and the influence of the substituent pattern on the photochemical reaction has been examined. Diastereoselectivity is observed when a double chiral induction strategy with dimenthyl helicene esters synthesized in a 70:30 ratio of isomers is used.
- Pearson, Morwenna S. M.,Carbery, David R.
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supporting information; experimental part
p. 5320 - 5325
(2009/11/30)
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- Addition of ArSSAr to dienes via intramolecular C-C bond formation initiated by a catalytic amount of ArS+
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A catalytic amount of electrochemically generated "ArS +" ("ArS+" = ArS(ArSSAr)+) initiates a cation chain reaction of dienes that involves the addition of ArSSAr associated with stereoselective intramolecular carbon-carbon bond formation, and the direct (in-cell) electrolysis of a mixture of a diene and ArSSAr with a catalytic amount of electricity also effectively initiates the reaction. The Royal Society of Chemistry 2009.
- Matsumoto, Kouichi,Fujie, Shunsuke,Suga, Seiji,Nokami, Toshiki,Yoshida, Jun-Ichi
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supporting information; experimental part
p. 5448 - 5450
(2009/12/08)
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- Highly efficient fluorine-promoted intramolecular condensation of benzo[c]phenanthrene: A new prospective on direct fullerene synthesis
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Various functional groups have been tested as alternative promoters of the intramolecular condensation of benzo-[c]phenanthrene under flash vacuum pyrolysis conditions. Methyl and fluorine functionalization were found to be promising approaches. Unexpectedly high selectivity was observed in the cyclization of fluorinated benzo[c]phenanthrenes. The mechanism for the condensation reaction and the advantages of fluorine as a promoter for the rational synthesis of fullerenes are discussed. Wiley-VCH Verlag GmbH & Co. KGaA.
- Amsharov, Konstantin Yu.,Kabdulov, Mikhail A.,Jansen, Martin
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experimental part
p. 6328 - 6335
(2011/03/19)
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- Further naphthylcombretastatins. An investigation on the role of the naphthalene moiety
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By synthesis and biological studies of new naphthalene analogues of combretastatins, we have found that the naphthalene is a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of combretastatin A-4, always generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxyphenyl moiety, the cytotoxic activity is largely decreased. The most cytotoxic naphthalene analogues of combretastatins, which also produce inhibition of tubulin polymerization, exerted their antimitotic effects through microtubule network disruption and subsequent G2/M arrest of the cell cycle in human cancer cells.
- Maya, Ana B. S.,Pérez-Melero, Concepción,Mateo, Carmen,Alonso, Dulce,Fernández, José Luis,Gajate, Consuelo,Mollinedo, Faustino,Peláez, Rafael,Caballero, Esther,Medarde, Manuel
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p. 556 - 568
(2007/10/03)
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- Unexpected interactions between sol-gel silica glass and guest molecules. Extraction of aromatic hydrocarbons into polar silica from hydrophobie solvents
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Properties of a solute may differ greatly between a free solution and that solution confined in pores of a sol-gel glass. We studied the entry of various aromatic organic compounds from solution into the monolith of sol-gel silica immersed in this solution. Partitioning of the solute is quantified by the uptake coefficient, the ratio of its concentrations in the glass and in the surrounding solution at equilibrium. The dependence of this coefficient on the solvent gives insight into possible interactions between the solute and the silica matrix. We report the uptake of 31 compounds altogether: 18 halogen derivatives of benzene; 5 condensed (fused) aromatics; and stilbene and three substituted derivatives of it, each in both cis and trans configurations. When the solvent is hexane, the uptake coefficients are as follows: 1.0-1.9 for the halobenzenes; 3.0-4.6 for the hydrocarbons; and 3.3-4.9 for the stilbenes. When the solvent is carbon tetrachloride or dichloromethane, the uptake coefficients become 0.82-1.39 for the hydrocarbons and 0.90-1.25 for the stilbenes. The excessive uptake of organic compounds from hexane is unexpected, for it amounts to extraction of nonpolar or slightly polar solutes from a nonpolar solvent into a polar interior of silica glass. The solute-silica interactions responsible for this extraction are not of the van der Waals type. Our findings are consistent with hydrogen bonding between the aromatic n system in the solutes and the hydroxyl groups on the silica surface. Hexane cannot interact with this surface but dichloromethane and carbon tetrachloride can: they shield the hydroxyl groups from the organic solvents and thus suppress the hydrogen bonding. This explanation is supported by the emission spectra of the aromatic compound pyrene when it is dissolved in acetonitrile, dichloromethane, cyclohexyl chloride, and hexane and when it is taken up by monoliths of sol-gel silica from these four solutions. The relative intensities of the emission bands designated III and I change greatly when pyrene is taken up from hexane but remain unchanged when it is taken up from the other three solvents. Evidently, hexane does not, whereas the other three solvents do, line the silica surface and shield it from approach by pyrene molecules. Even though solute molecules are much smaller than the pores in the sol-gel glass,.diffusion of these molecules into the monolith may result in an uneven partitioning at equilibrium. This fact must be taken into consideration in the design of biosensors, immobilized catalysts, and other composite materials because their function depends on the entry of analytes, substrates, and other chemicals into the glass matrix.
- Badjic, Jovica D.,Kostic, Nenad M.
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p. 11081 - 11087
(2007/10/03)
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- Wittig reactions on photoprotoporphyrin IX: New synthetic models for the special pair of the photosynthetic reaction center
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A first example of spirochlorin-chlorin dimer with fixed distances and orientations as potential model for the 'special pair' of the photosynthetic reaction center is discussed. For the preparation of such a novel structure, the Wittig reagent of the desired 'spacer' 5 was reacted with photoprotoporphyrin IX dimethyl ester 3 to produce the intermediate dimer 6, which on intramolecular [4 + 2] Diels-Alder cycloaddition gave an unexpected spirochlorin-chlorin dimer 9. Dehydration of dimer 6 under acid-catalyzed conditions generated the corresponding spirochlorinporphyrin dimer 16 in quantitative yield. The asymmetry in dimer 6 caused by the biphenyl-type anisotropic effect was confirmed by NMR and model studies. The formation of dihydrobenzoporphyrin 14 by reacting chlorin 3 with the phosphonium salt of p-methylbenzylbromide 10 and isolation of 8-phenanthrenevinylporphyrin 19 from chlorin 7 further confirmed our proposed mechanism for the formation of a spirochlorin-chlorin dimer 9. Following a similar approach, chlorin 3 on reacting with bis-phosphonium salt of 4,4'-bischloromethylbiphenyl produced conjugated chlorin dimer 25. The spectroscopic data obtained from these dimers suggest that, in these compounds, the individual chromophores are not behaving as an individual molecule, but as a single macrocycle. To examine whether the π-π interaction exhibited by dimer 9 resembles the structural arrangement of bacteriochlorophylls in reaction center (RC), we investigated the geometrical parameters used to characterize the π-π interactions in tetrapyrrolic macrocycles. Starting from the crystallographic coordinates of 9, the molecular mechanics energy minimization was performed to obtain the model dimer structure. The geometrical parameters that measure the single pyrrole ring overlap were used to compare the model structure with the crystallographic coordinates of the special pair in photosynthetic reaction center. The results indicated that the ring A of spirochlorin and the ring C of chlorin in our model dimer 9 mimic the ring A-ring A interaction found in the crystallographic special pairs, which are strategically placed by the surrounding photosynthetic reaction center protein matrix.
- Zheng, Gang,Shibata, Masayuki,Dougherty, Thomas J.,Pandey, Ravindra K.
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p. 543 - 557
(2007/10/03)
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- 4-hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: A novel, potent, and selective NR1/2B NMDA receptor antagonist
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A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC50 = 0.63 μM). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing cloned rat NMDA receptors. Side effect liability was assessed by measuring affinity for α1-adrenergic receptors and inhibition of neuronal K+ channels. Central bioavailability was gauged indirectly by determining anticonvulsant activity in a mouse maximal electroshock (MES) assay. Making progressive modifications to 8, a hydroxyl substituent on the phenyl ring para to the oxyethyl tether (10a) resulted in a ~25-fold increase in NR1A/2B potency (IC50 = 0.025 μM). p-Methyl substitution on the benzyl ring (10b) produced a ~3-fold increase in MES activity (ED50 = 0.7 mg/kg iv). Introduction of a second hydroxyl group into the C-4 position on the piperidine ring (10e) resulted in a substantial decrease in affinity for α1 receptors and reduction in inhibition of K+ channels with only a modest decrease in NR1A/2B and MES potencies. Among the compounds described, 10e (4- hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine, Co 101244/PD 174494) had the optimum pharmacological profile and was selected for further biological evaluation.
- Zhou, Zhang-Lin,Cai, Sui Xiong,Whittemore, Edward R.,Konkoy, Christopher S.,Espitia, Stephen A.,Tran, Minhtam,Rock, David M.,Coughenour, Linda L.,Hawkinson, Jon E.,Boxer, Peter A.,Bigge, Christopher F.,Wise, Lawrence D.,Weber, Eckard,Woodward, Richard M.,Keana, John F. W.
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p. 2993 - 3000
(2007/10/03)
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- Kinetic Study of the Substitution Reactions of Triphenylphosphine with Chlorobenzyl Chlorides, Dimethylbenzyl Chloride, and Methylbenzyl Bromides in Various Two-Phase Organic Solvent/Water Media
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The kinetics of the substitution reactions of triphenylphosphine (TP) with chlorobenzyl chlorides (CBC), 2,5-dimethylbenzyl chloride (DMBC), and methylbenzyl bromides (MBB) in aprotic organic solvent was studied under the extraction by water. The effects of water, agitation, organic solvent, reactant, and temperature were investigated. These reactions take place via the SN2 mechanism and exhibit large and negative entropy of activation. The order of relative activity of solvents is CHCl3 > CH2Cl2 >> C6H6. In CHCl3, the order of relative reactivity of benzyl chloride (BC), benzyl bromide (BB), CBC, DMBC, and MBB toward reaction with TP is 2-MBB > 4-MBB > 3-MBB > BB > DMBC > BC > 2-CBC > 4-CBC > 3-CBC. These reactions produce quantitatively benzyltriphenylphosphonium salts, which are useful for synthesizing Z-form isomers of stilbenes via the two-phase Wittig reaction.
- Shieh, Ruey-Lone,Lin, Ruey-Lih,Hwang, Jiann-Jyh,Jwo, Jing-Jer
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p. 517 - 523
(2007/10/03)
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- Ylidyl-dihalogenphosphane - Strukturbilder einer sich anbahnenden Dissoziation
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The reaction of phosphonium ylides with phosphorus trihalides has been studied for the synthesis of ylidyl-dihalophosphanes (= dihalophosphanyl ylides (Ph3P=CR-PX2 3, X = Cl, and 9, X = Br.Compounds 3, R = aryl, are readily prepared from the phosphonium bromides Br, compounds 3, R = alkyl, SiMe3 or PCl2, and 9 are obtained from silylylides Ph3P=CR-SiMe3, compound 3, R = PPh3(1+) results from the addition of PCl3 to the hexaphenylcarbodiphosphorane.A (β-morpholinovinyl)dichlorophosphane 12 has also been prepared.Ylides 3 are oxidized by sulfur and selenium and are converted to ylidyl-chlorophosphenium (= chlorophosphaalkenyl-phosphonium) salts AlCl4 10.In the 31P-NMR spectra of 3 and 9 the geminal coupling 2JPP indicates the phosphorus lone pair to be synperiplanar to the phosphonio group.In one case the P(III)-C rotation barrier has been estimated from VT-31P-NMR spectra.By X-ray crystallography the structures of 3, R = Me, 2,6-Cl2C6H4, 4-NO2C6H5, PCl2, of 9, R = Me (two molecules), SiMe3, of an ylidyl-selenophosphonyl dichloride (11b), and of 12 have been analyzed.They provide representatives for the full range of rotation from the symmetric conformer with two equal P-X bonds to the conformer with one P-X bond perpendicular to the PCP plane and with this bond being extremely elongated.Thus, they map out the pathway to P-X bond breaking.On this way the initial charge transfer from the ylidic carbon to the antibonding P-X orbital ends up in a ? donation and P-X dissociation. - Key Words: Ylides, dichloro- and dibromophosphanyl-/ Enamines, dichlorophosphanyl-/ Phosphonium ions, chlorophosphaalkenyl-/ Stereoelectronic (anomeric) effect and anionic hyperconjugation
- Schmidpeter, Alfred,Noeth, Heinrich,Jochem, Georg,Schroedel, Hans-Peter,Karaghiosoff, Konstantin
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p. 379 - 394
(2007/10/02)
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- Relative Reactivity and Stereoselectivity in the Wittig Reactions of Substituted Benzaldehydes with Benzylidenetriphenylphosphorane
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Carbonyl carbon-14 kinetic isotope effects and substituent effects on the relative reactivity and on the cis-trans product ratio were determined in the Wittig reaction of XC6H4CHO with Ph3P=CHC6H4Y in THF at 0 deg C.The isotope effect and the Hammett ρ value were positive under both Li salt-free (12k/14k = 1.060 +/- 0.003 and ρx = 2.77 +/- 0.15) and Li salt-present (12k/14k = 1.015 +/- 0.004 and ρx = 1.38 +/- 0.12) conditions, although they were much larger in the former case.These, together with the absence of enone isomerization for the benzylidene ylide reported previously, suggested that the reactions proceed via a polar cycloaddition transition state of considerable nucleophilic character.The cis-trans ratio of the product stilbene was essentially unchanged (40:60 in the salt-free and 60:40 in the Li salt-present reaction) by the change in concentration, the mode of addition, and the molar ratio of aldehyde and ylide, and it was varied only slightly for most substituents X and Y.However, the ratio was significantly varied when o-MeO or o-Cl was introduced as X.The results could be rationalized by assuming a chelating interaction between the lone pair of the ortho substituents and the phosphorous of the ylide.
- Yamataka, Hiroshi,Nagareda, Katsushi,Ando, Katsuhiro,Hanafusa, Terukiyo
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p. 2865 - 2869
(2007/10/02)
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- Untersuchungen im Wittig-System nach einem ordnenden Konzept auf der Basis alternativer Prinzipien
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Our results show that the stereoselectivity of the Wittig-reaction can be controlled by the variation of substituents in accord with the ORDERING CONCEPT OF ALTERNATIV PRINCIPLES (individual pairs, known and unknown classes of alternatives).The "all-phenyl Wittig-system" having three phenyl groups on phosphorous two in ylid- and aldehyd-position was chosen as a standard for our investigations.Differentiation in ylid-position and compensation on phosphorous and aldehyd-position were observed by the comparison of "patterns".Consequently, most of the selectivity rules of Wittig-reactions can be explained by the differentiation through alternatives in the ylid-position.Inversion or conservation of the "patterns" of measured data points to the variation in structure of starting materials, reaction rates and selectivities.Amount-controls were also described in certain systems.
- Bandmann, Heinz,Bartik, Tamas,Bauckloh, Sylvia,Behler, Ansgar,Brille, Frank,et al.
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p. 193 - 204
(2007/10/02)
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- Insecticidal alkenes
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Compounds of formula R3 --CH=CH--CR1 R2 --CH2 OCH2 R4 wherein R1 and R2 are H, alkyl or together form a cycloalkyl group with the adjacent carbon, R3 is a substituted phenyl group, R4 is an optionally subsituted phenoxy phenyl group, and compositions containing them useful as insecticides, and compounds of formula HOCH2 --CR1 R2 --CH2 OCH2 R4 and OCH--CR1 R2 CH2 OCH2 R4, useful as intermediates therefor.
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- Amidine derivatives and cardiotonic compositions
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Amidine derivatives of the formula STR1 wherein R1 and R2, which may be the same or different, represent each a hydrogen atom or a lower alkyl group, or R1 and R2 together with an intermediary carbon atom and/or hetero atom may form a ring; X represents STR2 (wherein R8 represents a hydrogen atom, a lower alkyl group, or --CH2 COOR9, where R9 represents a hydrogen atom or a lower alkyl group; Z represents a single bond, --CH2 --, --CH2 CH2 --, or --CH=CH--); R3 represents a hydrogen or chlorine atom, methoxy group, nitro group, or amino group; Y represents --CH2 CH2 --, --CH=CH--, --CH2 O--, or --OCH2 --; R4 represents a hydrogen atom, methoxy group, benzoyl group, nitro group, or amino group; and R5, R6 and R7, which may be the same or different, represent each a hydrogen atom, lower alkyl group, cycloalkyl group, aralkyl group, substituted alkyl group, substituted aralkyl group, or amino group, or R5 and R7 may form a ring, or salts thereof have an excellent cardiotonic activity and can be used as cardiotonics.
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- KINETICS AND LINEAR FREE ENERGY RELATIONSHIP OF WITTIG REACTION BETWEEN SUBSTITUTED BENZALDEHYDES AND SUBSTITUTED BENZYLIDENETRIPHENYLPHOSPHORANE
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Kinetics and linear free energy relationship (LFER) of Wittig reaction of ylides of intermediary stability have been investigated.Evidences are presented which indicate that under such cases the reaction follows a second order rate law, first order in phosphorane and aldehyde respectively, and furthermore that electron withdrawing substituents on both benzaldehyde and benzylidenetriphenylphosphorane impose rate enhancement effect upon the reaction.The mechanism of the reaction is discussed on the basis of the experimental findings
- Donxia, Li,Dexian, Wu,Yaozhong, Li,Huaming, Zhao
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p. 4161 - 4168
(2007/10/02)
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- Preparation of (E)-2-Hxdroxy-4'-Substituted Stilbenes
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Sixteen (E)-2-hydroxy-4'-substituted stilbenes have been prepared by the Wittig reaction.Direct coupling of the appropriate p-substituted benzylidenetriphenylphosphoranes with salicylaldehyde afforded the (E)-stilbenols (2) 4'-R = H(2a), Me(2b), But(2c), Ph(2d), CN(2e), NO2(2i), OMe(2k), F(2n), Cl(2o), and Br(2p).Alternatively, the Wittig reaction of o-methoxymethoxybenzylidenetriphenylphosphorane with various p-substituted benzaldehydes gave the (E)-methoxymethylstilbenols (4) which upon acidic cleavage furnished the corresponding stilbenols (2) 4'-R = CN(2e), CO2Me(2f), NMe2(2h), OH(2j), OAc(2m), and I(2q).The symmetrical (E)-2,2'-dihydroxystilbene was obtained in an analogous fashion.Reduction of nitrostilbenol (2i) yielded the corresponding aminostilbenol (2g).
- Mylona, Anastasia,Nikokavouras, John,Takakis, Ioannis M.
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p. 3514 - 3530
(2007/10/02)
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- Mechanisms of Arene Exchange in (Arene)tricarbonylchromium Compounds: Intermolecular and Intramolecular Exchanges in Complexes of Propenylbenzene, Stilbenes, and 1,1-Diphenylethylene
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Kinetic studies of arene exchange of (trans-propenylbenzene)tricarbonylchromium with benzene reveal intramolecular and intermolecular participation by the propenyl substituent.Intramolecular participation via direct bonding of Cr(CO)3 to the alkene portion of the ligand is supported by the observed "internal" exchange in Cr(CO)3 complexes of the three isomers of diphenylethene.The magnitudes of the internal exchange rate constants and the effect of added donor catalysts on internal exchange indicate that the geometry of the unsaturated hydrocarbon influences the movement of Cr(CO)3 along ? systems.
- Traylor T. G.,Stewart, Kevin J.
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p. 6977 - 6985
(2007/10/02)
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- Studies on Organic Fluorine Compounds. XLII. Synthesis and Reactions of Phenyltrifluoromethylacetylenes
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Phenyltrifluoromethylacetylene (4a) was synthesized by the pyrolysis of triphenylphosphonium α-(trifluoroacetyl)benzylide (3a), which was easily derived from benzyl halide (1a).This method can be used for the synthesis of 4-substituted-phenyltrifluoromethylacetylenes (4).The 1,3-dipolar reaction of 4 with diazomethane and phenyl azide proceeds readily to give trifluoromethylated pyrazoles and triazoles.Keywords - trifluoromethyl; acetylene; 1,3-dipolar reaction; intramolecular Wittig reaction; trifluoroacetylphosphonium ylide; pyrazole; diazomethane; phenyl azide
- Kobayashi, Yoshiro,Yamashita, Toshinori,Takahashi, Katsuhiro,Kuroda, Hisashi,Kumadaki, Itsumaro
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p. 4402 - 4409
(2007/10/02)
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- Carbon-Hydrogen vs. Carbon-Carbon Bond Cleavage of 1,2-Diarylethane Radical Cations in Acetonitrile-Water
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Radical cations of 1,2-diarylethanes and 1-phenyl-2-arylethanes (Ar = phenyl, p-tolyl, p-anisyl) were generated in acidic 70percent acetonitrile-water by Cu2+-catalyzed peroxydisulfate oxidation.The radical cations fragment mainly by loss of benzylic protons (C-H cleavage) rather than by alkyl C-C bond cleavage.The radical cation of 2,3-dimethyl-2,3-diphenylbutane fragments efficiently by C-C cleavage, forming cumyl radical and cumyl cation.Oxidations of bibenzyl-bicumyl mixtures show selective oxidation of bicumyl dependent on total substrate concentration, providing evidence of equilibrating radical cations and showing that bicumyl fragments faster than bibenzyl loses protons.The effects of reaction conditions and substrate structure on reactivity are discussed.
- Camaioni, Donald M.,Franz, James A.
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p. 1607 - 1613
(2007/10/02)
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