- Palladium(II)-Catalyzed Intramolecular C-H Alkenylation for the Synthesis of Chromanes
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The intramolecular Pd(II)-catalyzed alkenylation of aryl homoallyl ethers constitutes a mild, versatile, and efficient procedure for the synthesis of highly and diversely substituted chromanes and 2H-chromenes. The use of p-TsOH as an additive allows more efficient reactions that could be carried out a room temperature in most cases. The procedure has a wide scope, allowing the synthesis of alkylidenechromanes and 2H-chromenes substituted at C-2 or C-3 of the chromene moiety, thus accessing relevant flavenes and isoflavenes, and even coumarins, in high yields (59 to 91%, 32 examples).
- Carral-Menoyo, Asier,Misol, Alexander,Gómez-Redondo, Marcos,Sotomayor, Nuria,Lete, Esther
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- NO2 functionalized coumarin derivatives suppress cancer progression and facilitate apoptotic cell death in KRAS mutant colon cancer
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Colon cancer is one of the most lethal cancers worldwide even with the significant progress made in screening techniques and therapeutic agents. Genetic mutations in tumors complicated the treatments, and the survival rate remains low for patients at late or metastatic stages. KRAS gene mutation which leads to failure of the EGFR targeted therapies stands for an example of the challenges in clinical sites. Therefore, development of novel agents for colon cancer treatment is in need. Natural and synthetic coumarin derivatives have been suggested with various biological activities with pharmacologic potential including anti-cancer capacity. Here in this study, five coumarin derivatives, include trifluoromethyl-, dimethoxy-, and/or nitro-substitutions at different positions, were synthesized. Their cancer inhibition potential was investigated in various cancer cell lines. Our data demonstrated that one nitro-coumarin derivate, 5,7-Dimethoxy-4-methyl-6-nitro-chromen-2-one, exhibits cytotoxicity specifically towards colon cancer cells under competitive EC50. Our results showed that this compound can effectively suppress colon cancer cells harboring either wild type or mutant KRAS genes, and that it could inhibit short-term proliferation, long term proliferation, and migration capacities of cancer cells. Finally, we demonstrated that this coumarin derivate facilitates cancer cell death through activation of apoptosis pathway. Our results suggest that this coumarin derivate is a promising lead drug worth further investigation and development for future cancer treatment.
- Lin, Mei-Hsiang,Wang, Juo-Shan,Hsieh, Yi-Chen,Zheng, Jia-Huei,Cho, Er-Chieh
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- Nucleophilic substitution of hydrogen–the Boger reaction sequence as an approach towards 8-(pyridin-2-yl)coumarins
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5,7-Dimethoxy-8-(3,6-diphenylpyridin-2-yl)coumarins were obtained from 5,7-dimethoxycoumarins and 3,6-diphenyl-1,2,4-triazines via the protocol comprising aromatic SNH substitution in the triazine ring followed by the Boger transform
- Fatykhov, Ramil F.,Savchuk, Maria I.,Starnovskaya, Ekaterina S.,Bobkina, Maria V.,Kopchuk, Dmitry S.,Nosova, Emiliya V.,Zyryanov, Grigory V.,Khalymbadzha, Igor A.,Chupakhin, Oleg N.,Charushin, Valery N.,Kartsev, Viktor G.
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p. 299 - 300
(2019/06/13)
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- α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs
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Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2 CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p 50 values ranging between 11.084±0.117 to 145.24± 29.22 μg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2 -) at position 7 showed a remarkable (p 50 = 11.084±0.117 μg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 μg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.
- Singh, Parvesh,Ngcoya, Nomandla,Mopuri, Ramgopal,Kerru, Nagaraju,Manhas, Neha,Ebenezer, Oluwakemi,Islam, Md. Shahidul
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p. 127 - 135
(2018/03/21)
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- Palladium-Acid Co-Catalyzed Cleavage of Alkynoates to Construct Dibenzo[c,h]xanthene Derivatives
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A novel palladium-acid co-catalyzed C(sp)?C(sp2) cleavage of alkynoates for the construction of dibenzo[c,h]xanthene derivatives is reported. A catalytic amount of triflic acid (TfOH) afforded an efficient transformation into the final product. Furthermore, a reduction process of alkynoates was observed during the formation of dibenzo[c,h]xanthene, preliminary mechanistic studies indicated that the protonation of the new-formed methyl group in dibenzo[c,h]xanthene mainly came from water. (Figure presented.).
- Tang, Bo-Cheng,Wang, Miao,Ma, Jin-Tian,Wang, Zi-Xuan,Wu, Yan-Dong,Wu, An-Xin
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supporting information
p. 4023 - 4028
(2018/09/21)
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- Rh-Catalyzed Synthesis of Coumarin Derivatives from Phenolic Acetates and Acrylates via C-H Bond Activation
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An efficient annulation strategy involving the reaction of phenolic acetates with acrylates in the presence of [Rh2(OAc)4] as catalyst and formic acid as reducing agent, leading to the high yield synthesis of coumarin derivatives, has been developed. The addition of NaOAc as a base increased the yield of the products. The reaction is quite successful for both electron-rich as well as electron-deficient phenolic acetates, affording coumarins with excellent regioselectivity, and proceeds via C-H bond activation proven by deuterium incorporation studies.
- Gadakh, Sunita K.,Dey, Soumen,Sudalai, Arumugam
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p. 11544 - 11550
(2015/12/04)
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- FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis of 4-substituted coumarins. A useful complement to the Pechmann reaction
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The catalytic activity of FeCl3 for the synthesis of a variety of 4-substituted coumarins using high energy techniques has been investigated. The ultrasonic-assisted conditions provide a useful complement to the Pechmann reaction, affording the coumarin derivatives in excellent yields, under solvent-free conditions, in short reaction times using an inexpensive, mild and benign Lewis acid catalyst.
- Prousis, Kyriakos C.,Avlonitis, Nicolaos,Heropoulos, Georgios A.,Calogeropoulou, Theodora
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p. 937 - 942
(2014/02/14)
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- Multi-component one-pot synthesis of novel coumarinyldihydropyridines under solvent free conditions
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A library of fourteen 4-coumarinyl-1,4-dihydropyridines (coumarinyl-1,4-DHP) has been synthesized under modified Hantzsch 1,4-dihydropyridine synthesis condition by the condensation of 4-formylcoumarin, alkyl acetoacetate and ammonium acetate in the presence of Ba(NO 3)2 as a catalyst in 58 to 82% yields. Standardization of reaction conditions revealed that 10 mol% of Ba(NO3)2 is enough for optimum yields. The developed methodology does not require the use of organic solvents and hence makes the process eco-friendly. The structure of all the coumarinyl-1,4-DHPs were unambiguously eastablished on the basis of IR, 1H, 13C NMR spectroscopy and HRMS data analysis.
- Bohra, Kapil,Sharma, Deepti,Kumar, Banty,Olsen, Carl E.,Parmar, Virinder S.,Prasad, Ashok K.
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p. 1885 - 1891
(2014/01/17)
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- Synthesis of coumarins and neoflavones through zinc chloride catalyzed hydroarylation of acetylenic esters with phenols
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Acetylenic esters react with oxygenated phenols under solvent-free conditions in the presence of only 5 mol% of zinc chloride as a catalyst to give coumarins and neoflavones in reasonable-to-good yields. Georg Thieme Verlag Stuttgart. New York.
- Leao, Raquel A. C.,Def.demoraes, Paula,Pedro, Marcella C. B. C.,Costa, Paulo R. R.
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experimental part
p. 3692 - 3696
(2011/12/16)
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- Scandium(III) triflate-catalyzed coumarin synthesis
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Scandium(III) triflate is an excellent catalyst in the von Pechmann condensation. The solvent-free catalytic reactions proceed smoothly with a range of phenols and β-ketoesters in the presence of 10 mol% scandium(III) triflate at 80°C. This simple method affords various 4-substituted coumarins in good to excellent yield and is superior to the classical method in several aspects: solvent-free conditions, short reaction times, a decreased catalyst loading, a mild reaction temperature, and an easy workup. Copyright Taylor & Francis Group, LLC.
- Jung, Keumnyeo,Park, Yun-Jeong,Ryu, Jae-Sang
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experimental part
p. 4395 - 4406
(2009/04/11)
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- Formation of coumarins by palladium(II)-catalyzed reaction of phenols with ethyl acrylates
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The reaction of phenols with ethyl acrylates in the presence of a Pd(OAc)2 catalyst in trifluoroacetic acid did not yield dihydrocoumarins but gave coumarins, in contrast to the reaction of phenols with propiolates. The addition of K2S2O8 as an oxidant increased the yield of coumarins. The reaction of several phenols with ethyl cinnamate, ethyl crotonate, or ethyl acrylate gave the corresponding coumarin derivatives in moderate to good yields. The coumarin formation competed with the oxidative coupling of electron-rich phenols, which reduced the product yield.
- Aoki, Shinya,Oyamada, Juzo,Kitamura, Tsugio
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p. 468 - 472
(2007/10/03)
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- Synthesis of coumarins catalyzed by heterobimetallic Co/Rh nanoparticles
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Described here is the use of cobalt/rhodium (CO2Rh2) heterobimetallic nanoparticles in the catalytic synthesis of coumarins via cyclocarbonylation of alkynes with 2-iodophenol under 1 atm of carbon monoxide and reaction of phenol wit
- Park, Kang Hyun,Jung, Il Gu,Chung, Young Keun
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p. 2541 - 2544
(2007/10/03)
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- ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free conditions
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Zirconium (IV) chloride is used as an efficient catalyst in the Pechmann condensation reaction of phenols with β-keto esters leading to the formation of coumarin derivatives in good yields under solvent-free conditions.
- Smitha,Reddy, Ch. Sanjeeva
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p. 3997 - 4003
(2007/10/03)
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- PdII-Catalyzed Reaction of Phenols with Propiolic Esters. A Single-Step Synthesis of Coumarins
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The intermolecular reaction of phenols with propiolic esters in TFA in the presence of a Pd(OAc)2 catalyst, affording coumarin derivatives, is described. An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin was observed in the reaction of 3,4,5-trimethoxyphenol and ethyl phenylpropiolate with a catalytic amount of Pd(OAc)2. The reaction in the absence of Pd(OAc)2 did not give any coumarin at all. Coumarin derivatives were obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethoxyphenol. Furthermore, the reaction of some phenols with various 2-alkynoates or with diethyl acetylenedicarboxylate gave the corresponding coumarins in good-to-high yields.
- Kitamura, Tsugio,Yamamoto, Kiyomi,Kotani, Masashi,Oyamada, Juzo,Jia, Chengguo,Fujiwara, Yuzo
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p. 1889 - 1895
(2007/10/03)
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- Atom economy. Palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a net C-H insertion
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A strategy to achieve ortho substitution of phenols initiated by an ortho-palladation to create coumarins was examined. Indeed, treatment of alkynoates with electron-rich phenols in the presence of a palladium catalyst and an acid does generate coumarins. The scope of the reaction with respect to the phenol and the alkynoates is defined. With unsymmetrical aromatic substrates, generally good regioselectivity that reflects the HOMO coefficients can be observed. In the course of these studies, numerous important naturally occurring coumarins have been synthesized, including fraxinol methyl ether, ayapin, herniarin, xanthoxyletin, and alloxanthoxyletin. The fact that a Pd(0) is the precatalyst rather than a Pd(+2) species and that an acid that reduces Pd(+2) salts, formic acid, functions better than other carboxylic acids raises doubts about the initial working hypothesis. A novel mechanism involving a palladium phenoxide formed from a hydridopalladium carboxylate and phenol is invoked to rationalize the results.
- Trost, Barry M.,Toste, F. Dean,Greenman, Kevin
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p. 4518 - 4526
(2007/10/03)
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- Direct synthesis of coumarins by Pd(II)-catalyzed reaction of alkoxyphenols and alkynoates
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Reaction of alkoxyphenols and alkynoates in the presence of a catalytic amount of Pd(OAc)2 in trifluoroacetic acid at room temperature gave coumarin derivatives in high yields. This procedure provides a convenient method for direct synthesis of coumarin derivatives under very mild conditions.
- Oyamada, Juzo,Jia, Chengguo,Fujiwara, Yuzo,Kitamura, Tsugio
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p. 380 - 381
(2007/10/03)
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- Synthesis of Highly Functionalized Flavones and Chromones Using Cycloacylation Reactions and C-3 Functionalization. A Total Synthesis of Hormothamnione
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The cycloacylations of hydroxy- and methoxy-substituted phenols with aryl- and alkylpropiolic acids using Eaton's reagent (10percent phosphorus pentoxide in methanesulfonic acid) gives highly substituted flavones and chromones in up to 63 percent yield.Styrylchromones were prepared from 2-methylchromones by condensation reactions of the 2-methyl group with various substituted benzaldehydes in sodium ethoxide and ethanol in almost quantitative yield.Methylation or hydroxylation at C-3 of these highly substituted flavones and styrylchromones was accomplished in a highly regioselective manner employing lithium diisopropylamide followed by quenching with an electrophile.Quenching of the initial anion with methyl triflate gave 3-methyl products while quenching of the initial anion with trimethylborate followed by oxidation gave 3-hydroxy products.A total synthesis of the naturally occurring styrylchromone hormothamnione, containing a 3-methyl substituent, is reported by use of these synthetic techniques.
- McGarry, Lynda W.,Detty, Michael R.
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p. 4349 - 4356
(2007/10/02)
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- 13C Nuclear Magnetic Resonance Spectroscopy of 4-Methylcoumarins (4- Methyl-2H-1-benzopyran-2-ones)
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The 13C NMR spectra of 36 differently substituted 4-methylcoumarins (4-methyl-2H-1-benzopyran-2-ones) have been recorded.The effects of an alkyl side-chain at C-3 on the chemical shift values and that of a methoxy or an acetoxy group in place of a hydroxy group have been observed and rationalized.This study may be helpful in the structure elucidation of nei and natural 4-methylcoumarins. KEY WORDS 13C NMR chemical shifts 4-Methylcoumarins 4-Methyl-2H-1-benzopyran-2-ones.
- Parmar, V. S.,Singh, S.,Boll, P. M.
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p. 430 - 433
(2007/10/02)
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- PREPARATION D'α-OXY-ALKYL-4 COUMARINES, MODELES D'INSECTICIDES NATURELS
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The synthesis of 4-(α-hydroxy-alkyl)-5,7-dihydroxy coumarins as analogs of insecticidal coumarins is described.Oxidation through SeO2 or bromination by crown-ether catalysed substitution provide the functionalization of the 4-alkyl chain.Both reactions depend on the substitution of the phenolic groups.
- Ramiandrasoa, F.,Kunesch, N.,Kunesch, G.,Poisson, J.
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p. 177 - 180
(2007/10/02)
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