- Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues
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Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol.
- Bjornstal, Olaf T.,Du, Liqin,Jemal, Mauricio A.,Kerwin, Sean M.,Lee, Dallas,Rodebaugh, Mary,Schwartz, Zachary T.,Shelton, Spencer D.,Theisen, Peter D.,Zhao, Zhenze
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- Design, synthesis and antibacterial activity against pathogenic mycobacteria of conjugated hydroxamic acids, hydrazides and O-alkyl/O-acyl protected hydroxamic derivatives
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With the aim to discover new antituberculous molecules, three novel series of 23 hydroxamic acids, 13 hydrazides, and 9O-alkyl/O-acyl protected hydroxamic acid derivatives have been synthesized, and fully characterized by spectral 1H NMR,
- Canaan, Stéphane,Cavalier, Jean-Fran?ois,Magrioti, Victoria,Mallick, Ivy,Mavrikaki, Vasiliki,Pagonis, Alexandros,Poncin, Isabelle
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supporting information
(2022/03/27)
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- Oxoammonium-Mediated Allylsilane–Ether Coupling Reaction
-
A new C(sp3)?H functionalization reaction consisting of the oxidative α-allylation of allyl- and benzyl- methyl ethers has been developed. The C?C coupling could be carried out under mild conditions thanks to the use of cheap and green oxoammonium salts. The scope of the reaction was studied over 27 examples, considering the nature of the substituents on the two coupling partners.
- Carlet, Federica,Bertarini, Greta,Broggini, Gianluigi,Pradal, Alexandre,Poli, Giovanni
-
supporting information
p. 2162 - 2168
(2021/04/02)
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- Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades
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We report a dramatic effect on product outcomes of the lithium ion enabled amino-Cope-like anionic asymmetric cascade when different γ-dienolate heteroatom substituents are employed. For dienolates with azide, thiomethyl, and trifluoromethylthiol substituents, a Mannich/amino-Cope/cyclization cascade ensues to form chiral cyclohexenone products with two new stereocenters in an anti-relationship. For fluoride-substituted nucleophiles, a Mannich/amino-Cope cascade proceeds to afford chiral acyclic products with two new stereocenters in a syn-relationship. Bromide- and chloride-substituted nucleophiles appear to proceed via the same pathway as the fluoride albeit with the added twist of a 3-exo-trig cyclization to yield chiral cyclopropane products with three stereocenters. When this same class of nucleophiles is substituted with a γ-nitro group, the Mannich-initiated cascade is now diverted to a β-lactam product instead of the amino-Cope pathway. These anionic asymmetric cascades are solvent- and counterion-dependent, with a lithium counterion being essential in combination with etheral solvents such as MTBE and CPME. By altering the geometry of the imine double bond from E to Z, the configurations at the R1 and X stereocenters are flipped. Mechanistic, computational, substituent, and counterion studies suggest that these cascades proceed via a common Mannich-product intermediate, which then proceeds via either a chair (X = N3, SMe, or SCF3) or boat-like (X = F, Cl, or Br) transition state to afford amino-Cope-like products or β-lactam in the case of X = NO2.
- Das, Pradipta,Delost, Michael D.,Qureshi, Munaum H.,Bao, Jianhua,Fell, Jason S.,Houk, Kendall N.,Njardarson, Jon T.
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supporting information
p. 5793 - 5804
(2021/05/07)
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- Mizoroki-Heck Reaction of Unstrained Aryl Ketones via Ligand-Promoted C-C Bond Olefination
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Mizoroki-Heck reaction of unstrained aryl ketone with acrylate/styrene is accomplished via palladium-catalyzed ligand-promoted C-C bond cleavage. Various (hetero)aryl ketones are compatible in the reaction, affording the alkene product in good to excellent yields. Further applications in the late-stage olefination of some drugs, natural products, and fragrance-derived aryl ketones demonstrate the synthetic utility of this protocol. By employing ketone as both the directing group and the leaving group, 1,2-bifunctionalization is achieved via sequential ortho-C-H alkylation/ipso-Heck olefination.
- Wang, Mei-Ling,Xu, Hui,Li, Han-Yuan,Ma, Biao,Wang, Zhen-Yu,Wang, Xing,Dai, Hui-Xiong
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supporting information
p. 2147 - 2152
(2021/04/05)
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- Design, synthesis, trypanocidal activity, and studies on human albumin interaction of novel s-alkyl-1,2,4-triazoles
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Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 μmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.
- Franklim, Tatiany N.,Freire-De-Lima, Leonardo,Chaves, Otávio A.,LaRocque-De-Freitas, Isabel F.,da Silva-Trindade, Joana D.,Netto-Ferreira, José C.,Freire-De-Lima, Célio G.,Decoté-Ricardo, Debora,Previato, José O.,Mendon?a-Previato, Lucia,De Lima, Marco E.F.
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p. 1378 - 1394
(2019/08/26)
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- The Catalytic Asymmetric Mukaiyama–Michael Reaction of Silyl Ketene Acetals with α,β-Unsaturated Methyl Esters
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α,β-Unsaturated esters are readily available but challenging substrates to activate in asymmetric catalysis. We now describe an efficient, general, and highly enantioselective Mukaiyama–Michael reaction of silyl ketene acetals with α,β-unsaturated methyl esters that is catalyzed by a silylium imidodiphosphorimidate (IDPi) Lewis acid.
- Gatzenmeier, Tim,Kaib, Philip S. J.,Lingnau, Julia B.,Goddard, Richard,List, Benjamin
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supporting information
p. 2464 - 2468
(2018/02/06)
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- Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin
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Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic de
- Saavedra, Diana I.,Rencher, Benjamin D.,Kwon, Doo-Hyun,Smith, Stacey J.,Ess, Daniel H.,Andrus, Merritt B.
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p. 2018 - 2026
(2018/02/23)
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- Synthesis of Analogs of Trans-Fagaramide and Their Cytotoxic Activity
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A series of 30 compounds were synthetized inspired by active trans-fagaramide structure skeleton. On this synthetic platform, 18 compounds were achieved via Knoevenagel condensation using maleic acid and piperonal, followed by peptide coupling with various amines, giving an average yield of 54%. Subsequently, nine compounds were obtained by palladium-mediated Heck coupling with an average yield of 79%. In addition, cytotoxic activity was evaluated against cardiomyoblast H9c2, breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2, and glioblastoma U-87 cells. The results revealed two aryl halogen-substituted compounds moderately active against H9c2 and MCF7 with IC50 values > 50 μM. One functionalized coumarin showed inhibitory activity against H9c2 (IC50 > 50 μM). In contrast, p-aminophenyl-β-monosubstituted trans-fagaramide was found to inhibit MCF7 (IC50 > 50 μM) without showing toxicity against H9c2 cells.
- Tomas, Melissa Barrera,Shiao, Tze Chieh,Nguyen, Phuong Trang,Bourgault, Steve,Roy, René
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p. 995 - 1004
(2018/02/22)
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- Transition-Metal-Free Stereocomplementary Cross-Coupling of Diols with Boronic Acids as Nucleophiles
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The transition-metal-free diastereoselective C(sp2)-C(sp3) cross-coupling between unprotected diols and boronic acids or potassium organotrifluoroborates is reported. Depending on the reaction conditions, the syn or the anti reaction products are obtained in a stereocomplementary fashion. This type of coupling is developed with alkenyl-, heteroaryl- and arylboron compounds as carbon nucleophiles.
- Ortega, Víctor,Del Castillo, Estefanía,Csák?, Aurelio G.
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supporting information
p. 6236 - 6239
(2017/11/24)
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- 4-Alkyliden-azetidinones modified with plant derived polyphenols: Antibacterial and antioxidant properties
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Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene-azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial-antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2–8 μg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC-ABTS being significantly more active than Trolox.
- Giacomini, Daria,Musumeci, Rosario,Galletti, Paola,Martelli, Giulia,Assennato, Lorenzo,Sacchetti, Gianni,Guerrini, Alessandra,Calaresu, Enrico,Martinelli, Marianna,Cocuzza, Clementina
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p. 604 - 614
(2017/10/10)
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- Tandem catalysis: Versus one-pot catalysis: Ensuring process orthogonality in the transformation of essential-oil phenylpropenoids into high-value products via olefin isomerization-metathesis
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Conversion of essential-oil allylbenzenes (phenylpropenoids) to high-value fine chemicals via isomerization-metathesis is reported. The target reaction sequence involves isomerization of ArCH2CH=CH21 into the corresponding conjugated olefins 2, and ensuing cross-metathesis with acrylates to generate ArCH=CHCO2R 3. The second-generation Hoveyda catalyst HII was chosen for the metathesis step. A range of lead candidates was assessed for the isomerization step, of which most active was the Grotjahn catalyst [CpRu(PN)(MeCN)]PF6([4]PF6; PN = 2-PiPr2-4-tBu-1-Me-imidazole). The following order of isomerization activity was determined, using the isomerization of estragole 1a to anethole 2a (Ar = p-MeOC6H4) as a probe reaction: [CpRu(PN)(MeCN)]PF6> RuHCl(CO)(PPh3)3> Ru(Me-allyl)2(COD) > Pd2Br2(PtBu3)2> RuHCl(PPh3)3> RuCl3(μ2-C)(μ2,κ1-C,η6-Mes-H2IMes)Ru(H)(H2IMes) (the "Grubbs hydride") > RuHCl(CO)(H2IMes)(PCy3) > RuHCl(CO)(IMes)(PCy3) > RuHCl(CO)(PCy3)2. To maximize process efficiency, a systematic comparison of orthogonal tandem catalysis versus sequential catalyst addition was undertaken, using catalysts [4]PF6and HII. The impact of each process type on product selectivity and catalyst compatibility was assessed. Selectivity was undermined in tandem isomerization-metathesis by competing metathesis of 1. Sequential catalyst addition eliminated this problem. The isomerization catalyst [4]PF6adversely affected metathesis yields when equimolar with HII, an effect traced to the imidazole functionality in [4]PF6. However, at the low catalyst loadings required for efficient isomerization (0.1 mol% [4]PF6), negligible impact on metathesis yields was evident. The target cinnamates and ferrulates were obtained in quantitative yields by coupling these steps in a one-pot isomerization-metathesis protocol.
- Higman, Carolyn S.,De Araujo,Fogg, Deryn E.
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p. 2077 - 2084
(2016/04/26)
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- Ligand-controlled regiodivergent palladium-catalyzed decarboxylative allylation reaction to access α,α-difluoroketones
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α,α-Difluoroketones possess unique physicochemical properties that are useful for developing therapeutics and probes for chemical biology. To access the α-allyl-α,α-difluoroketone substructure, complementary palladium-catalyzed decarboxylative allylation reactions were developed to provide linear and branched α-allyl-α,α-difluoroketones. For these orthogonal processes, the fluorination pattern of the substrate enabled the ligands to dictate the regioselectivity of the transformations.
- Yang, Ming-Hsiu,Orsi, Douglas L.,Altman, Ryan A.
-
supporting information
p. 2361 - 2365
(2015/03/04)
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- METHODS OF TREATMENT USING ARYLCYCLOPROPYLAMINE COMPOUNDS
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Described herein are methods of treating breast cancer using arylcyclopropylamine compounds.
- -
-
Paragraph 0303-0304; 0311
(2014/12/09)
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- Intramolecular dehydro-diels-alder reaction affords selective entry to arylnaphthalene or aryldihydronaphthalene lignans
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Intramolecular dehydro-Diels-Alder (DDA) reactions are performed affording arylnaphthalene or aryldihydronaphthalene lactones selectively as determined by choice of reaction solvent. This constitutes the first report of an entirely selective formation of arylnaphthalene lactones utilizing DDA reactions of styrene-ynes. The synthetic utility of the DDA reaction is demonstrated by the synthesis of taiwanin C, retrohelioxanthin, justicidin B, isojusticidin B, and their dihydronaphthalene derivatives. Computational methods for chemical shift assignment are presented that allow for regioisomeric lignans to be distinguished.
- Kocsis, Laura S.,Brummond, Kay M.
-
supporting information
p. 4158 - 4161
(2014/09/29)
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- METHODS OF TREATMENT USING ARYLCYCLOPROPYLAMINE COMPOUNDS
-
Described herein are methods of treating Parkinson's disease using arylcyclopropylamine compounds.
- -
-
Paragraph 0221; 0222; 0229
(2013/07/19)
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- Part I: The development of the catalytic wittig reaction
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We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96 %) by using a precatalyst loading of 4-10 mol %. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74 % yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions. A point of difference: By utilizing an organosilane to chemoselectively reduce a phosphane oxide precatalyst to a phosphane (see scheme), the first catalytic (in phosphane) Wittig reaction has been developed. The methodology has been applied to the synthesis of 22 disubstituted and 24 trisubstituted olefins, including a multigram synthesis of a precursor to the anti-Alzheimer drug donepezil hydrochloride.
- O'Brien, Christopher J.,Nixon, Zachary S.,Holohan, Andrew J.,Kunkel, Stephen R.,Tellez, Jennifer L.,Doonan, Bryan J.,Coyle, Emma E.,Lavigne, Florie,Kang, Lauren J.,Przeworski, Katherine C.
-
supporting information
p. 15281 - 15289
(2013/11/06)
-
- Asymmetric synthesis of 1-aza-4-deoxypicropodophyllotoxin
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In our search for new easily accessible analogues based on the natural product podophyllotoxin, we synthesized 1-aza-4-deoxypicropodophyllotoxin in good overall yield and excellent enantioselectivity. The synthesis was centered around a direct asymmetric Mannich reaction using d-proline as the key step for introduction of the chiral centres. Our synthesis of 1-aza-4- deoxypodophyllotoxin was hindered through the increased instability towards epimerization of the C2 position. We did, however, synthesized a new scaffold based on the opened lactone analogue. Georg Thieme Verlag Stuttgart New York.
- Aigret, Benoit M.,Jacobs, Jeroen,Van Meervelt, Luc,De Borggraeve, Wim M.
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p. 1097 - 1100
(2013/06/27)
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- Chemical plants: High-value molecules from essential oils
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As society faces a future of dwindling petrochemical supplies at increasing cost, much attention has been focused on methods to degrade biomass into renewable commodity-chemical building blocks. Reported here is a powerful complementary approach that amplifies the complexity of molecular structures present in plant materials. Essential-oil phenylpropenoids are transformed via acrylate cross-metathesis into potent antioxidants that are widely used in perfumery and cosmetics, and in treating disorders associated with oxidative damage.
- Lummiss, Justin A. M.,Oliveira, Kelley C.,Pranckevicius, Alexandre M. T.,Santos, Alexandra G.,Dos Santos, Eduardo N.,Fogg, Deryn E.
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supporting information
p. 18889 - 18891
(2013/01/15)
-
- AGONISTS THAT ENHANCE BINDING OF INTEGRIN-EXPRESSING CELLS TO INTEGRIN RECEPTORS
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A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal.
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Page/Page column 42-43
(2012/06/01)
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- Amides from Piper capense with CNS activity - A preliminary SAR analysis
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Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.
- Pedersen, Mikael E.,Metzler, Bjorn,Stafford, Gary I.,Van Staden, Johannes,Jaeger, Anna K.,Rasmussen, Hasse B.
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experimental part
p. 3833 - 3843
(2009/12/26)
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- Stereoselective synthesis of 3-alkyl-2-aryltetrahydrofuran-4-ols: Total synthesis of (±)-paulownin
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(Chemical Equation Presented) A formal [3 + 2]-cycloaddition involving the Lewis acid mediated reaction of α-silyloxy aldehydes and styrenes to afford 3-alkyl-2-aryltetrahydrofuran-4-ols has been developed. This methodology was applied to the total synthesis of the naturally occurring furofuran lignan (±)-paulownin.
- Angle, Steven R.,Choi, Inchang,Tham, Fook S.
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p. 6268 - 6278
(2008/12/22)
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- ANTI CANCER USE OF CAFFEIC ACID AND DERIVATIVES
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The present invention relates to the use of caffeic acid or a derivative thereof represented by the following general formula (1 ) wherein X is O, NH, or heterocyclyl; R may be present or absent and if present, is H, alkyl, aryl, or heterocyclyl; in all its stereoisomeric and tautomeric forms, and mixtures thereof in all ratios, and a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, pharmaceutically acceptable polymorph or a prodrug, in the treatment of chronic myeloid leukemia (CML) which is resistant to treatment with Gleevec. The invention also relates to a method for reducing the proliferation of cells that are resistant to Gleevec by contacting the cells with a compound of general formula (1 ). The present invention also relates to pharmaceutical compositions (for the manufacture of the medicament) including caffeic acid or a derivative or a salt thereof represented by the general formula (1 ) for the treatment of chronic myeloid leukemia (CML) that is resistant to treatment with Gleevec, or for reducing the proliferation of cells that are resistant to Gleevec. The present invention further relates to a method of treatment of chronic myeloid leukemia (CML) that is resistant to treatment with Gleevec.
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Page/Page column 17
(2008/06/13)
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- An efficient chemoselective strategy for the preparation of (E)-cinnamic esters from cinnamaldehydes using heterogeneous catalyst and DDQ
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An efficient chemoselective protocol is developed for the synthesis of (E)-cinnamic esters from substituted cinnamaldehydes or cinnamyl alcohols using a combination of DDQ and heterogeneous catalyst under microwave irradiation. The method showed remarkable selectivity for cinnamaldehydes over aliphatic and aromatic aldehydes, which is a novel finding. The results demonstrate that the developed protocol can be a useful synthetic tool for chemoselective esterification in total synthesis of complex organic compounds.
- Sinha, Arun K.,Sharma, Anuj,Swaroop, Anand,Kumar, Vinod
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p. 1000 - 1007
(2007/10/03)
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- Treatment of skin conditions
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The present invention provides piperine and analogues or derivatives thereof for the treatment of skin conditions treatable by stimulation of melanocyte proliferation, such as vitiligo, and also for treating skin cancer. The piperine and analogues or derivatives thereof may also be used to cosmetically promote or enhance the natural coloration of the skin.
- -
-
-
- A highly stereospecific synthesis of (E)-α,β-unsaturated esters
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CrCl2-induced olefination of aldehydes using methyl dichloroacetate exclusively generates (E)-α,β-unsaturated esters in excellent yields. The intermediate α-chloro-β-hydroxy adducts could also be isolated in good yields under conditions of limited reagent.
- Barma, Deb K.,Kundu, Asish,Bandyopadhyay, Anish,Kundu, Abhijit,Sangras, Bhavani,Briot, Anne,Mioskowski, Charles,Falck
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p. 5917 - 5920
(2007/10/03)
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- Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation
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A wide range of piperine analogues has been synthesised in order to undertake a structure-activity study of their ability to stimulate melanocyte proliferation. Results demonstrate that an aromatic ring containing at least one ether function and a carbonyl group containing side chain is essential for this activity. A number of highly active piperine analogues have been identified, for instance 1-(3,4-methylenedioxyphenyl)-penta-2E,4E-dienoic acid methyl ester (5a), 1-E,E-piperinoyl-isobutylamine (4f) and 1-(3,4- methylenedioxyphenyl)-pentanoic acid cyclohexyl amide (20). A selection of analogues has also been evaluated for their effect on melanocyte morphology and melanogenesis. The piperine analogues altered cell morphology by increasing dendrite formation leading to bi-, tri- and quadripolar cells. These same analogues were found to increase total melanin in cell cultures, although melanin content per cell was not significantly altered from control in the presence of these compounds.
- Venkatasamy, Radhakrishnan,Faas, Laura,Young, Antony R.,Raman, Amala,Hider, Robert C.
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p. 1905 - 1920
(2007/10/03)
-
- Treatment of skin conditions
-
The present invention provides piperine and analogues or derivatives thereof for the treatment of skin conditions treatable by stimulation of melanocyte proliferation, such as vitiligo, and also for treating skin cancer. The piperine and analogues or derivatives thereof may also be used to cosmetically promote or enhance the natural coloration of the skin.
- -
-
-
- Treatment of skin conditions
-
The present invention provides piperine and analogues or derivatives thereof for the treatment of skin conditions treatable by stimulation of melanocyte proliferation, such as vitiligo, and also for treating skin cancer. The piperine and analogues or derivatives thereof may also be used to cosmetically promote or enhance the natural coloration of the skin.
- -
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-
- Three-component synthesis of (E)-α,β-unsaturated amides of the piperine family
-
Selective formation of (E)-α,β-unsaturated amides by intermolecular three-component reaction between aldehydes, amines (1° or 2°) and ketenylidenetriphenylphosphorane (Ph3P=C=C=O) is described. Natural amides such as fagaramide and piperines could be prepared from immediately available educts. The method is shown to be extendable to the preparation of thioesters from thiols and aldehydes.
- Schobert,Siegfried,Gordon
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p. 2393 - 2397
(2007/10/03)
-
- Syntheses of certain 3-aryl-2-propenoates and evaluation of their cytotoxicity
-
A series of 3-aryl-2-propenoates including cinnamates, (E)-methyl/ethyl 3-[2-(1,4-dimethoxy-5,8-dione)naphthalenyl]-2-propenoates (8ba, 8bb) and (E)-methyl/ethyl 3-[2-(1,4-dihydroxy-9,10-dione)anthracenyl]-2-propenoates (9aa, 9ab) was synthesized and eval
- Nam, Nguyen-Hai,You, Young-Jae,Kim, Yong,Hong, Dong-Ho,Kim, Hwan-Mook,Ahn, Byung Zun
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p. 1173 - 1176
(2007/10/03)
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- Enzyme-assisted asymmetric total synthesis of (-)-podophyllotoxin and (- )-picropodophyllin
-
Described is the first catalytic, asymmetric synthesis of (-)- podophyllotoxin and its C2-epimer, (-)picropodophyllin. Asymmetry is achieved via the enzymatic desymmetrization of advanced meso diacetate 20, through PPL-mediated ester hydrolysis. A second key feature of the synthesis is the strategically late introduction of the highly oxygenated natural ring E through an arylcopper species. The successful implementation of this approach augers well for the introduction of other functionalized rings E for future SAR work. The synthesis begins from piperonal, which is fashioned into isobenzofuran (IBF) precursor 14 in three steps (bromination, acetalization, and halogenmetal exchange/hydroxymethylation). Interestingly, treatment of 14 with HOAc in commerical dimethyl maleate (contains 5% dimethyl fumarate) leads to a nearly equimolar mixture of fumarate-(15) and maleate-IBF Diels- Alder adducts (16 and 17), indicating that IBF 11 reacts about 15 times faster with dimethyl fumarate than with dimethyl maleate. With scrupulously pure dimethyl maleate a 2.8:1 endo:exo mixture of maleate DA adducts is still obtained. On the other hand, the desired meso diester 16 is obtained pure and in nearly quantitative yield by employing neat dimethyl acetylene dicarboxylate as the dienophile, followed by catalytic hydrogenation. Reduction (LiAlH4) of 16 provides meso diol 19, which is then treated with Ac2O, BzCl, and PhCH2COCl to provide the corresponding meso diesters, 20- 22. Screening of these meso benzoxabicyclo[2.2.1]heptyl substrate candidates across a battery of acyl transfer enzymes leads to an optimized match of diacetate 20 with PPL. Even on 10-20 g scales, asymmetry is efficiently introduced here, yielding the key chiral intermediate, monoacetate 25 (66% isolated yield, 83% corrected yield, 95% ee). Protecting group manipulation and oxidation (Swern) provide aldehyde 27b, which undergoes efficient retro- Michael ring opening to produce dihydronaphthalene 30, in which the C3 and C4 stereocenters are properly set. Following several unsuccessful approaches to the intramolecular delivery of ring E (via Claisen rearrangement, Heck- type cyclization, or radical cyclization), a highly diastereoselective, intermolecular conjugate addition of the arylcopper reagent derived from (3,4,5-trimethoxy)phenylmagnesium bromide and CuCN to acyl oxazolidinone 50 was developed (85% yield, only the required α-stereochemistry at C1 is observed). The conjugate addition product is converted to (-)- picropodophyllin in two steps (lactonization, SEM deprotection) or to (-)- podophyllotoxin, in three steps, through the introduction of a C2- epimerization step, under Kende conditions, prior to the final conjugate addition.
- Berkowitz, David B.,Choi, Sungjo,Maeng, Jun-Ho
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p. 847 - 860
(2007/10/03)
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- Microwave enhanced esterification of α,β-unsaturated acids
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A rapid and efficient method for the synthesis of α,β-unsaturated esters by the esterification of the corresponding carboxylic acids using dry methanol in the presence of catalytic amount of concentrated sulphuric acid under microwave irradiation is reported.
- Mitra,De,Karchaudhuri
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p. 311 - 312
(2007/10/03)
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- Organophosphorus chemistry 32. 1 The reaction of vanillin, ortho-vanillin and piperonal with stabilized methylenetriphenylphosphoranes (wittig reagents)
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Vanillin (1) and piperonal (3) reacted with ylidenetriphenylphosphoranes 4a-f in boiling toluene following the Wittig mechanism to give the ethylenes 5a-f and 7a-f. Similarly, ethylenes 8c-f were produced when ortho-vanillin (2) was allowed to react with 4c-f. The reaction of aldehyde (2) with the P-ylides 4a,b yielded the Wittig products 8a,b and 8-methoxycoumarin (10). Triphenylphosphine oxide (TPPO, 6) was isolated and identified in all cases. The mechanism for formation of 10 was discussed. Structural reasonings for all new compounds were based upon compatible elementary as well as spectroscopic (IR, 1H-NMR and MS) measurements.
- Hafez, Taghrid S.,Henary, Maged M.,Mahran, Mohamed Refat H.
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- PALLADIUM-CATALYZED ARYLATION OF OLEFINS BY 1,2-(METHYLENEDIOXY)-4-BROMOBENZENE
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1,2-(Methylenedioxy)-4-bromobenzene reacts with acrylic, methacrylic, crotonic, 2-hexenoic, cinnamic, maleic, and fumaric esters, acrylonitrile, and methyl vinyl ketone and gives the corresponding β-ar
- Dashkina, L. R.,Kulak, A. N.,Kasatkin, A. N.,Zorin, V. V.,Rakhmankulov, D. L.,Beletskaya, I. P.
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p. 422 - 426
(2007/10/02)
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- PHASE-TRANSFER CATALYZED ALKYLATIVE ELIMINATION OF METHYL 2-PHENYLSULFINYLACETATE. A ONE-POT SYNTHESIS OF SUBSTITUTED CINNAMATES
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The facile alkylative elimination of the anion of methyl 2-phenylsulfinylacetate under solid-liquid phase-transfer conditions is described.Application of this one-pot method to the synthesis of ring-substituted cinnamates is presented.
- Chong-ying, Xu,Guang-jian, Liu,Zhen, Zhang
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p. 1839 - 1844
(2007/10/02)
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- BIOSYNTHESIS OF PODOPHYLLUM LIGNANS - I. CINNAMIC ACID PRECURSORS OF PODOPHYLLOTOXIN IN PODOPHYLLUM HEXANDRUM
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Feeding experiments in Podophyllum hexandrum plants have established that phenylalanine, cinnamic acid and ferulic acid are good precursors of the two major aryltetralin lignans podophyllotoxin and 4'-demethylpodophyllotoxin.Sinapic and 3,4,5-trimethoxycinnamic acids were poorly utilized, showing that the substitution pattern of the pendent aryl ring is built up after coupling of the two phenylpropane units.Degradation studies on podophyllotoxin derived from ferulic acid show that the two halves of the lignan molecule are equally labelled supporting a biosynthetic sequence involving oxidative coupling of two similar phenylpropane precursors having the substitution pattern of ferulic acid.Although 3,4-methylenedioxycinnamic acid was readily incorporated, degradative studies prove that this compound is not incorporated intact, but via a metabolic sequence in which the methylenedioxy carbon atom enters the C1-pool and then labels the methylenedioxy and methoxyl substituents of podophyllotoxin.The rest of the skeleton is incorporated via ferulic acid, presumably by way of caffeic acid.Key Word Index - Podophyllum hexandrum; Podophyllaceae; aryltetralin; lignans; biosynthesis; podophyllotoxin.
- Jackson, David E.,Dewick, Paul M.
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p. 1029 - 1036
(2007/10/02)
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- NEW PHENOLIC ETHERS FROM ESSENTIAL OILS OF SOME RUTACEAE
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Two phenolic ethers were isolated from the essential oils of some Agathosma species.Structures elucidated by spectral analysis and synthesis were trans-1,2-methylenedioxy-4-(3'-methoxy-1'-propenyl)benzene and trans-1,2-dimethoxy-4-(3'-methoxy-1'-propenyl)
- Campbell, William E.,George, Peter
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p. 1455 - 1456
(2007/10/02)
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