- Salvianolic acid I: A new depside from Salvia cavaleriei
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A new depside named salvianolic acid I was isolated from the aqueous extract of Salvia cavaleriei, along with salvianolic acids A, B, C, H, isosalvianolic acid C, lithospermic acid, and rosmarinic acid. The chemical structures were determined by spectral
- Zhang,Li
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- A TETRACYCLIC TRITERPENE LACTONE AND OTHER CONSTITUENTS FROM THE BARK OF ABIES FIRMA
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The stem bark of Abies firma contained five n-fatty acids having C22-C26, campesterol, β-sitosterol, five n-alkyl ferulates bearing alkyl groups from C22 to C26 and a new tetracyclic triterpene lactone, for which the structure was established as 3-oxo-9β-lanosta-7,24-dien-26,23R-olide by single crystal X-ray analysis.
- Tanaka, Reiko,Inosiri, Atsuyo,Yoneda, Michiko,Ishida, Toshimasa,Numada, Atsushi,et al.
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- Characterization by LC-MSn of four new classes of chlorogenic acids in green coffee beans: Dimethoxycinnamoylquinic acids, diferuloylquinic acids, caffeoyl-dimethoxycinnamoylquinic acids, and feruloyl- dimethoxycinnamoylquinic acids
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LC-MS4 has been used to detect and characterize in green coffee beans 12 chlorogenic acids not previously reported in nature. These comprise three isomeric dimethoxycinnamoylquinic acids (7-9) (Mr 382), three caffeoyl-dimethoxycinnam
- Clifford, Michael N.,Knight, Susan,Surucu, Birgul,Kuhnert, Nikolai
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Read Online
- Pd-Catalyzed desulfitative arylation of olefins by: N -methoxysulfonamide
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A novel Pd-catalyzed protocol for the desulfitative Heck-type reaction of N-methoxy aryl sulfonamides with alkenes was reported. The cross-coupling reaction was performed successfully with a variety of olefins to obtain aryl alkenes. Different substituents on the aromatic ring of N-methoxysulfonamides were also found to be compatible with the reaction conditions. Expectedly, the reaction proceeds through CuCl2-promoted generation of the nitrogen radical and subsequent desulfonylation under thermal conditions to afford the aryl radical for the Pd-catalyzed coupling reaction. N-Methoxysulfonamide was further exploited for the synthesis of symmetrical biaryls in the presence of CuCl2. This journal is
- Ojha, Subhadra,Panda, Niranjan
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supporting information
p. 1292 - 1298
(2022/02/19)
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- Covalent Inhibition of Bacterial Urease by Bifunctional Catechol-Based Phosphonates and Phosphinates
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In this study, a new class of bifunctional inhibitors of bacterial ureases, important molecular targets for antimicrobial therapies, was developed. The structures of the inhibitors consist of a combination of a phosphonate or (2-carboxyethyl)phosphinate functionality with a catechol-based fragment, which are designed for complexation of the catalytic nickel ions and covalent bonding with the thiol group of Cys322, respectively. Compounds with three types of frameworks, including β-3,4-dihydroxyphenyl-, α-3,4-dihydroxybenzyl-, and α-3,4-dihydroxybenzylidene-substituted derivatives, exhibited complex and varying structure-dependent kinetics of inhibition. Among irreversible binders, methyl β-(3,4-dihydroxyphenyl)-β-(2-carboxyethyl)phosphorylpropionate was observed to be a remarkably reactive inhibitor of Sporosarcina pasteurii urease (kinact/KI = 10 420 s-1 M-1). The high potential of this group of compounds was also confirmed in Proteus mirabilis whole-cell-based inhibition assays. Some compounds followed slow-binding and reversible kinetics, e.g., methyl β-(3,4-dihydroxyphenyl)-β-phosphonopropionate, with Ki? = 0.13 μM, and an atypical low dissociation rate (residence time τ = 205 min).
- Pagoni, Aikaterini,Grabowiecka, Agnieszka,Tabor, Wojciech,Mucha, Artur,Vassiliou, Stamatia,Berlicki, ?ukasz
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supporting information
p. 404 - 416
(2021/01/13)
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- Design and synthesis of dual active neovibsanin derivatives based on a chemical structure merging method
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A hybrid compound consisting of neovibsanin and trans-banglene was designed according to a structure merging method and synthesized via a sequence of key steps including a Diels–Alder cycloaddition, stereoselective alkynylation, and intramolecular oxa-Mic
- Fukuyama, Yoshiyasu,Imagawa, Hiroshi,Kasai, Yusuke,Kishimoto, Suguru,Kubo, Miwa,Matsui, Nobuaki,Yamamoto, Hirofumi,Yanagimoto, Tsuyoshi
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supporting information
(2020/08/19)
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- Enantioselective Total Syntheses of Pallambins A–D
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The first enantioselective total syntheses of (?)-pallambins A–D have been achieved in 15 or 16 steps from a known chiral cyclohexenone. Salient features of the syntheses include a palladium-catalyzed oxidative cyclization to assemble the [3.2.1]bicyclic moiety, an Eschenmoser–Claisen rearrangement/lactone formation sequence to construct the C ring, an intramolecular Wittig reaction to form the D ring, and individual transformations of pallambins C and D to generate pallambins A and B. The described synthesis avoids protecting-group manipulations through the design of highly chemo- and stereoselective transformations. During the course of this work, a palladium-catalyzed method for the dehydrobromination of α-bromoketones was developed, and the scope of this transformation was also investigated.
- Zhang, Xiwu,Cai, Xinxian,Huang, Bin,Guo, Lei,Gao, Zhongrun,Jia, Yanxing
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p. 13380 - 13384
(2019/08/16)
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- Natural product derivatization with β-lactones, β-lactams and epoxides toward ‘infinite’ binders
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β-Lactones, β-lactams and epoxides are privileged structural motifs found in both therapeutics and natural products. Herein we report several strategies for annulation of these motifs onto natural products that are not known to covalently modify their cellular targets. These strategies can facilitate identification of previously unidentified cellular targets or identify novel cellular targets of these natural products. The reported strategies include telescoped synthesis of β-lactones from allylic alcohols, nucleophile-catalyzed Michael aldol-β-lactonizations, and [2 + 2] β-lactam annulations with complex, commercially available alkene-containing natural products as substrates. A novel method for the tagging of phenolic natural products with epoxides is also reported.
- Jouanneau, Morgan,Vellalath, Sreekumar,Kang, Guowei,Romo, Daniel
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supporting information
p. 3348 - 3354
(2019/05/17)
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- In-vitro and in-vivo antimalarial activity of caffeic acid and some of its derivatives
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Objectives: To explore the in-vitro and in-vivo antimalarial potential of caffeic acid and derivatives. Methods: Two common phenolic acids (caffeic acid and chlorogenic acid) were evaluated for in-vitro and in-vivo antiplasmodial activity in comparison with some semi-synthetic derivatives that were synthesized. An in-vitro assay based on plasmodial lactate dehydrogenase activity, and the classical in-vivo 5-day suppressive test from Peters on an artemisinin-resistant Plasmodium berghei strain was used. Parasitic stage sensitivity to ethyl caffeate was determined in this work. Key findings: Phenolic acid esters derivatives showed better antiplasmodial activity than corresponding phenolic acids. The derivative with the highest in-vitro activity being caffeic acid ethyl ester, exhibiting an IC50?=?21.9?±?9.4?μm. Ethyl caffeate and methyl caffeate were then evaluated for antimalarial activity in?vivo and ethyl caffeate showed a growth inhibition of 55% at 100?mg/kg. Finally, it seems that ethyl caffeate blocks the growth of young parasitic forms. Conclusions: Our study provides evidence for an antimalarial potential of caffeic acid derivatives which are common in several medicinal plants traditionally used against malaria. It also demonstrates the possibility to use such derivatives in the treatment of malaria.
- Alson, Sylvain G.,Jansen, Olivia,Cieckiewicz, Ewa,Rakotoarimanana, Hajatiana,Rafatro, Herintsoa,Degotte, Gilles,Francotte, Pierre,Frederich, Michel
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p. 1349 - 1356
(2018/07/31)
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- SCAPHOPETALONE ANALOGS AND THEIR USES
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The present disclosure relates to scaphopetalone analogs, methods of making the analogs, and their medicinal uses.
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Page/Page column 24
(2017/05/10)
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- Synthesis, antiviral activity, and molecular docking study of trans-ferulic acid derivatives containing acylhydrazone moiety
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In this study, we report the synthesis and antiviral activity of trans-ferulic acid derivatives containing acylhydrazone moiety. Biological tests demonstrated that most target compounds showed potent antiviral activity against tobacco mosaic virus (TMV). Compound D4 showed remarkable inactivating activity with EC50 value of 36.59 μg/mL, which was obviously superior to ribavirin (126.05 μg/mL). Molecular docking results revealed that compound D4 exhibited the optimal combining capacity with five hydrogen bonds to different amino-acid residues of TMV coat protein (TMV-CP). Docking results were consistent with the inactivating activity of target compounds against TMV.
- Wang, Zhenzhen,Xie, Dandan,Gan, Xiuhai,Zeng, Song,Zhang, Awei,Yin, Limin,Song, Baoan,Jin, Linhong,Hu, Deyu
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p. 4096 - 4100
(2017/08/23)
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- A kind of carboxylic acid with malonic acid method of esterification reaction of dimethyl ester (by machine translation)
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The invention belongs to the field of chemical synthesis and particularly relates to a carboxyl acid compound methyl etherification method. The carboxyl acid compound methyl etherification method comprises the following steps: in a polar solvent, using a carboxyl acid compound and dimethyl malonate as reactants, under the catalysis of a catalyst, and preparing an acid methyl ester compound through the methyl etherification reaction of the carboxyl acid. The method has the advantages of cheap raw materials, easiness in raw material acquisition, low toxicity, high safety, simple neutral salt catalyst and low dosage and is suitable for industrial application.
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Paragraph 0046; 0047
(2017/02/28)
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- A Mixed-Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B
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A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) r
- Panish, Robert A.,Chintala, Srinivasa R.,Fox, Joseph M.
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supporting information
p. 4983 - 4987
(2016/04/26)
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- (-)-Tarchonanthuslactone: Design of New Analogues, Evaluation of their Antiproliferative Activity on Cancer Cell Lines, and Preliminary Mechanistic Studies
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Natural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total syntheses of dihydropyran-2-ones modeled on the structure of 1 were undertaken. These compounds were obtained in overall yields of 17-21 % based on the Keck asymmetric allylation reaction and were evaluated in vitro against eight different cultured human tumor cell lines. We further conducted initial investigation into the mechanism of action of selected analogues. Dihydropyran-2-one 8 [(S,E)-(6-oxo-3,6-dihydro-2H-pyran-2-yl)methyl 3-(3,4-dihydroxyphenyl)acrylate], a simplified analogue of (-)-tarchonanthuslactone (1) bearing an additional electrophilic site and a catechol system, was the most cytotoxic and selective compound against six of the eight cancer cell lines analyzed, including the pancreatic cancer cell line. Preliminary studies on the mechanism of action of compound 8 on pancreatic cancer demonstrated that apoptotic cell death takes place mediated by an increase in the level of reactive oxygen species. It appears as though compound 8, possessing two Michael acceptors and a catechol system, may be a promising scaffold for the selective killing of cancer cells, and thus, it deserves further investigation to determine its potential for cancer therapy. Fighting the big C: We describe the synthesis of a new family of analogues based on the scaffold of the natural product (-)-tarchonanthuslactone; these compounds were evaluated in vitro against tumor cell lines. We further conducted an initial investigation into the mechanism of action, including the inhibition of phosphatases and glutathione-S-transferase and the production of reactive oxygen species.
- Toneto Novaes, Luiz Fernando,Martins Avila, Carolina,Pelizzaro-Rocha, Karin Juliane,Vendramini-Costa, Débora Barbosa,Pereira Dias, Marina,Barbosa Trivella, Daniela Barreto,Ernesto De Carvalho, Jo?o,Ferreira-Halder, Carmen Veríssima,Pilli, Ronaldo Aloise
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supporting information
p. 1687 - 1699
(2015/10/06)
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- The palladium slow-release pre-catalysts and nanoparticles in the "phosphine-free" Mizoroki-Heck and Suzuki-Miyaura reactions
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The Mizoroki-Heck reaction of electronrich aryl iodides was studied using a phosphine-free catalytic system with a broad range of pre-catalysts of varied stability and structure based on organoselenium chelators. The application of the "mercury test" by observing the response of the catalytic systems studied not only to the addition, but also to the withdrawal of Hg allowed us to establish a critical role of nanoparticles in the operation of the phos-phine-free catalytic systems. A three-stage mechanistic scheme involving a slow stage served by mononuclear Pd species, and the main fast stage served by Pd nanoparticles, and terminated by the nanoparticle decay is proposed as a general mechanistic paradigm for the phosphine-free Mizoroki-Heck and the related Suzuki-Miyaura reactions.
- Sigeev, Alexander S.,Peregudov, Alexander S.,Cheprakov, Andrei V.,Beletskaya, Irina P.
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supporting information
p. 417 - 429
(2015/02/19)
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- A practical, chemoselective approach to O-methylation of carboxylic acids with dimethyl malonate
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A practical and chemoselective method is described for the O-methylation of carboxylic acids. Dimethyl malonate, a low toxic and commercially available compound was found to be an effective methylating reagent for a variety of carboxylic acids affording methyl ester products in good to high yields and with excellent chemoselectivity, without the use of strong bases as additives. A mechanism involving the utilization of potassium bromide is tentatively proposed.
- Mao, Jincheng,Liu, Defu,Li, Yongming,Zhao, Jinzhou,Rong, Guangwei,Yan, Hong,Zhang, Guoqi
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p. 9067 - 9072
(2015/11/09)
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- Total synthesis of tubastrine and 3-dehydroxy tubastrine by microwave-assisted cross-coupling reactions
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The first syntheses of tubastrine and 3-dehydroxy tubastrine are described. The target compounds were prepared in four consecutive steps from commercially available starting materials. The central scaffold was formed by a microwave-assisted C-N cross-coupling reaction between 1,3-bis(tert-butoxycarbonyl)-guanidine and (E)-((4-(2-iodovinyl)-1,2-phenylene)bis(oxy))bis(tert-butyldimethylsilane) and (E)-tert-butyl(4-(2-iodovinyl)phenoxy)-dimethylsilane, respectively. The aryl vinyl iodides were obtained by a Hunsdiecker-Borodin-type reaction of aryl acrylic acids, which were easily available from trans-caffeic acid or trans-p-coumaric acid.
- Lorentzen, Marianne,Bayer, Annette,Sydnes, Magne O.,J?rgensen, K?re B.
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p. 8278 - 8284
(2015/10/05)
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- Fe(TAML)Li/(diacetoxyiodo)benzene-mediated oxidation of alcohols: Evidence for mild and selective C-O and C-C oxidative cleavage in lignin model transformations
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A novel combination of Fe(TAML)Li and (diacetoxyiodo)- benzene for the oxidation of primary and secondary alcohols at 25 °C in acetone is reported. In view of the interesting ability of this system to selectively cleave specific types of C-C bonds of elaborated alcohols, the application of this novel combination to the oxidative cleavage of lignin model molecules was investigated. Considering the numerous supported versions of the oxidant as well as the mild conditions employed, the developed methodology appears to be a promising lignin depolymerization strategy.
- Napoly, Francois,Jean-Gerard, Ludivine,Goux-Henry, Catherine,Draye, Micheline,Andrioletti, Bruno
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supporting information
p. 781 - 787
(2014/03/21)
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- Synthesis and leishmanicidal activity of cinnamic acid esters: Structure-activity relationship
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Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 15-17, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 12-17); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 18-20 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.
- Otero, Elver,Robledo, Sara M.,Diaz, Santiago,Carda, Miguel,Munoz, Diana,Panos, Julian,Velez, Ivan D.,Cardona, Wilson
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p. 1378 - 1386
(2014/03/21)
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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.
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supporting information
p. 4158 - 4161
(2014/09/29)
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- Synthesis and DPPH radical scavenging activity of novel compounds obtained from tyrosol and cinnamic acid derivatives
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Tyrosol, a naturally occurring phenolic compound poorly attractive as an antioxidant because of its weak efficacy, was used as starting material to obtain novel compounds. The synthesis is based on a trifluoroacetic acid-mediated hydroarylation of cinnamic esters with tyrosol to produce 4-aryl-3,4-dihydrocoumarins, molecules of biological interest, followed by a basic hydrolysis to give the corresponding ring opening products. Unreported mechanistic investigations confirmed that the first step resulted from an electrophilic aromatic substitution and an intramolecular transesterification. Final products exhibited DPPH radical scavenging activity significantly higher than tyrosol.
- Barontini, Maurizio,Bernini, Roberta,Carastro, Isabella,Gentili, Patrizia,Romani, Annalisa
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p. 809 - 816
(2014/02/14)
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- Inhibitory effects of substituted cinnamic acid esters on mushroom tyrosinase
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A series of substituted cinnamic acid esters were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. Compound 8 was found to be the most potent inhibitor with IC 50 value of 5.60μM. Preliminary structure activity relationships (SARs) were concluded. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed that compound 8 was anti-competitive inhibitor.
- Zhang, Zhenghua,Liu, Jinbing,Wu, Fengyan,Zhao, Liangzhong
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p. 529 - 534
(2013/07/26)
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- Synthesis and antimicrobial activities of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins
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A new series of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins were synthesized by the reaction of substituted cinnamic acids and 3-arylpropiolic acid with the corresponding phenols. These compounds were evaluated for antibacterial activity in vitro. The
- Sun, Jie,Ding, Wei-Xian,Hong, Xiao-Ping,Zhang, Ke-Yun,Zou, Yong
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experimental part
p. 16 - 22
(2012/07/28)
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- Metabolism of methylisoeugenol in liver microsomes of human, rat, and bovine origin
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Methylisoeugenol (1,2-dimethoxy-4-propenylbenzene, 1) is a minor constituent of essential oils, naturally occurring as a mixture of cis/trans isomers. 1 is a U.S. Food and Drug Administration-approved food additive and has been given "Generally Recognized as Safe" status. Previously, metabolism of 1 has been studied in the rat, revealing mainly nontoxic cinnamoyl derivatives as major metabolites. However, data concerning the possible formation of reactive intermediary metabolites are not available to date. In this study, the oxidative metabolism of 1 was studied using liver microsomes of rat [not induced, rat liver microsomes (RLM); Aroclor1254 induced RLM (ARLM)], bovine, and human (pooled from 150 donors) origin. Incubations of these microsomes with 1 provided phase I metabolites that were separated by high-performance liquid chromatography (HPLC) and identified by NMR and UV-visible spectroscopy and/or liquid chromatography-mass spectrometry. Identity was confirmed by comparison with 1H NMR spectra of synthesized reference compounds. Formation of metabolites was quantified by HPLC/UV using dihydromethyleugenol (10) synthesized as the internal standard. From incubations of ARLM with 1, seven metabolites could be detected, with 3′- hydroxymethylisoeugenol (2), isoeugenol and isochavibetol (3 + 4), and 6-hydroxymethylisoeugenol (5) being the main metabolites. Secondary metabolites derived from 1 were identified as the α,β-unsaturated aldehyde 3′-oxomethylisoeugenol (6) and 1′,2′-dihydroxy- dihydromethylisoeugenol (7). We were surprised to find that formation of allylic 6-hydroxymethyleugenol (8) was observed starting at approximately 30 min after the beginning of incubations with ARLM. HLM did not form ring-hydroxylated metabolites but were most active in the formation of 6 and 7. ARLM incubations displayed the highest turnover rate and broadest metabolic pattern, presumably resulting from an increased expression of cytochrome P450 enzymes. In conclusion, we present a virtually complete pattern of nonconjugated microsomal metabolites of 1 comprising reactive metabolites and suggest the formation of reactive intermediates that need more investigation with respect to their possible adverse properties. Copyright
- Cartus, Alexander T.,Merz, Karl-Heinz,Schrenk, Dieter
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experimental part
p. 1727 - 1733
(2012/03/22)
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- Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors
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Because of the complex cascade of molecular events that can occur in the brain of an Alzheimer's disease (AD) patient, the therapy of this neurodegenerative disease seems more likely to be achieved by multifunctional drugs. Herein, a new series of dual-targeting ligands have been developed and in vitro bioevaluated. Their architecture is based on conjugating the acetylcholinesterase inhibition and anti-oxidant properties in one molecular entity. Specifically, a series of naturally occurring phenolic acids with recognized anti-oxidant properties (derivatives of caffeic acid, rosmarinic acid, and trolox) have been conjugated with choline to account for the recognition by acetylcholinesterase (AChE). The synthesized hybrid compounds evidenced AChE inhibitory capacity of micromolar range (rationalized by molecular modeling studies) and good antioxidant properties. Their effects on human neuroblastoma cells, previously treated with beta-amyloid peptides and 1-methyl-4-phenylpyridinium ion neurotoxins (to simulate AD and Parkinson's disease, respectively), also demonstrated a considerable capacity for protection against the cytotoxicity of these stressors.
- Sebestik, Jaroslav,Marques, Sergio M.,Fale, Pedro L.,Santos, Susana,Arduino, Daniela M.,Cardoso, Sandra M.,Oliveira, Catarina R.,Serralheiro, M. Luisa M.,Santos, M. Amelia
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experimental part
p. 485 - 497
(2012/05/19)
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- OXADIAZOLE COMPOUNDS, THEIR PREPARATION AND USE
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The present invention relates to oxadiazole compounds in all their stereoisomeric and tautomeric forms and mixtures thereof in all ratios; and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs and pharmaceutically acceptable polymorphs. The invention also relates to processes for the manufacture of the oxadiazole compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the treatment of cancer, particularly chronic myeloid leukemia (CML). The present invention further provides a method of treatment of cancer by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof.
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- Tandem allylic oxidation-condensation/esterification catalyzed by silica gel: An expeditious approach towards antimalarial diaryldienones and enones from natural methoxylated phenylpropenes
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A new one-pot strategy has been developed, wherein abundantly available methoxylated phenylpropenes are directly transformed into corresponding dienones (1,5-diarylpenta-2,4-dien-1-ones) and enones (chalcones and cinnamic esters) via allylic oxidation-condensation or allylic oxidation-esterification sequences. Preliminary antimalarial activity studies of the above synthesized diaryldienones and enones against Plasmodium falciparum (Pf3D7) have shown them to be promising lead candidates for developing newer and economical antimalarial agents. In particular, two enones (12b and 13b) were found to possess comparatively better activity (IC50 = 4.0 and 3.4 μM, respectively) than licochalcone (IC50 = 4.1 μM), a well known natural antimalarial compound. The Royal Society of Chemistry 2011.
- Sharma, Abhishek,Sharma, Naina,Shard, Amit,Kumar, Rakesh,Mohanakrishnan, Dinesh,Saima,Sinha, Arun K.,Sahal, Dinkar
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p. 5211 - 5219
(2011/08/07)
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- ANALOGUES OF ANTI-FIBROTIC AGENTS
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The present invention relates to analogues of anti-fibrotic agents having the formula (I) with the substituents as described within the specification. The present invention also relates to methods for their preparation.
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Page/Page column 46-47
(2010/12/31)
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- An efficient route to xanthine based A2A adenosine receptor antagonists and functional derivatives
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A one-pot route to 8-substituted xanthines has been developed from 5,6-diaminouracils and carboxaldehydes. Yields are good and the process applicable to a range of substrates including a family of A2A adenosine receptor antagonists. A new route to the KW-6002 family of antagonists is presented including a pro-drug variant, and application to related image contrast agents developed.
- Labeaume, Paul,Dong, Ma,Sitkovsky, Michail,Jones, Elizabeth V.,Thomas, Rhiannon,Sadler, Sara,Kallmerten, Amy E.,Jones, Graham B.
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supporting information; experimental part
p. 4155 - 4157
(2010/10/21)
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- Enantioselective synthesis and antioxidant activity of 3-(3,4- dihydroxyphenyl)-glyceric acid - Basic monomeric moiety of a biologically active polyether from Symphytum asperum and S. caucasicum
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The racemic and enantioselective synthesis of a novel glyceric acid derivative, namely, 2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid as well as the antioxidant activities is described. The virtually pure enantiomers, (+)-(2R,3S)-2,3-dihydroxy-3-(3
- Merlani, Maia,Barbakadze, Vakhtang,Amiranashvili, Lela,Gogilashvili, Lali,Yannakopoulou, Elina,Papadopoulos, Kyriakos,Chankvetadze, Bezhan
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experimental part
p. 717 - 725
(2010/11/16)
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- Polymer-assisted solution-phase synthesis under combined ultrasound and microwave irradiation: Preparation of α,β-unsaturated esters and carboxylic acids, key intermediates of novel sigma ligands
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The optimal conditions to prepare α,β-unsaturated methyl esters via Wittig reaction combining polymer-assisted solution-phase synthesis (PASPS) methodology and simultaneous ultrasound and microwave irradiation were established. The effects of temperature, solvent, and irradiation time were discussed. Results clearly indicated the superiority of combined ultrasound and microwave-assisted procedure over microwave-assisted methodology. Moreover, an efficient PASPS procedure to prepare α,β-unsaturated carboxylic acids via tandem Wittig olefination and hydrolysis reaction was developed under combined ultrasound and microwave irradiation. Generally, a good conversion of aldehydes to acids was observed. The optimized protocols allowed us to quickly prepare a small collection of either α,β-unsaturated esters or carboxylic acids, key intermediates for the drug-discovery process of new sigma ligands. Copyright Taylor & Francis Group, LLC.
- Rossi,Urbano,Baraglia, A. Carnevale,Serra,Bergamelli,Iannelli,Azzolina,Collina
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experimental part
p. 3254 - 3262
(2011/03/18)
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- COMPOUNDS WITH (SUBSTITUTED PHENYL)-PROPENAL MOIETY, THEIR DERIVATIVES, BIOLOGICAL ACTIVITY, AND USES THEREOF
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The present invention includes compounds, pharmaceuticals and cosmetics having at least one (substituted phenyl)-propenal moiety. The compounds and compositions of the present invention are useful in the treatment or prevention of many medical conditions such as androgen associated conditions. The present invention also includes methods of treating a medical condition including an androgen associated condition, using at least one of the disclosed compounds.
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Page/Page column 27-28; 30
(2008/12/07)
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- Structure-activity relationships of phenylpropanoids as antifeedants for the pine weevil Hylobius abietis
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Ethyl cinnamate has been isolated from the bark of Pinus contorta in the search for antifeedants for the pine weevil, Hylobius abietis. Based on this lead compound, a number of structurally related compounds were synthesized and tested. The usability of the Topliss scheme, a flow diagram previously used in numerous structure-activity relationship (SAR) studies, was evaluated in an attempt to find the most potent antifeedants. The scheme was initially followed stepwise; subsequently, all compounds found in the scheme were compared. In total, 51 phenylpropanoids were tested and analyzed for SARs by using arguments from the field of medicinal chemistry (rational drug design). Individual Hansch parameters based on hydrophobicity, steric, and electronic properties were examined. The effects of position and numbers of substituents on the aromatic ring, the effects of conjugation in the molecules, and the effects of the properties of the parent alcohol part of the esters were also evaluated. It proved difficult to find strong SARs derived from single physicochemical descriptors, but our study led to numerous new, potent, phenylpropanoid antifeedants for the pine weevil. Among the most potent were methyl 3-phenylpropanoates monosubstituted with chloro, fluoro, or methyl groups and the 3,4-dichlorinated methyl 3-phenylpropanoate.
- Bohman,Nordlander,Nordenhem,Sunnerheim,Borg-Karlson,Unelius
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p. 339 - 352
(2008/09/18)
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- Structure-antifungal activity relationship of cinnamic acid derivatives
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A structure-antifungal activity relationship (SAR) study of 22 related cinnamic acid derivatives was carried out. Attention was focused on the antifungal activities exhibited against Aspergillus flavus, Aspergillus terreus, and Aspergillus niger. (E)-3-(4-Methoxy-3-(3-methylbut-2-enyl)phenyl)acrylic acid (16) exhibited antifungal activity against A. niger, comparable to that of miconazole and a significant antifungal effect against A. flavus and A. terreus as well. A structure-activity relationship (SAR) study of related cinnamic acid derivatives has allowed a model to be proposed for the recognition of the minimal structural requirements for the antifungal effect in this series.
- Bisogno, Fabricio,Mascoti, Laura,Sanchez, Cecilia,Garibotto, Francisco,Giannini, Fernando,Kurina-Sanz, Marcela,Enriz, Ricardo
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experimental part
p. 10635 - 10640
(2009/11/30)
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- Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors
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Dihydroxy stilbene derivatives were designed based on lithospermic acid B and were prepared from 4-(chloromethyl)benzoic acid. The inhibitory activities of the novel compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated. 3,4-Dihydroxy stilbene carbonyl compounds (7, 11b, 27b) inhibited PTP1B with IC50 values comparable to molybdate, while the conjugation-extended compound (15b) showed inhibition 3-fold better than preclinical RK682. The introduction of electron withdrawing groups or amides into the second phenyl ring, or extension of the conjugation into the stilbene molecule may increase stability of the generated radicals.
- Jung, Mankil,Lee, Yongnam,Park, Moonsoo,Kim, Hanjo,Kim, Heekyeong,Lim, Eunyoung,Tak, Jungae,Sim, Minjoo,Lee, Dongeun,Park, Namsoo,Oh, Won Keun,Hur, Kyu Yeon,Kang, Eun Seok,Lee, Hyun-Chul
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p. 4481 - 4486
(2008/02/13)
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- Quantitative structure-activity relationships of pine weevil antifeedants, a multivariate approach
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Antifeedant activity of mainly phenylpropanoic, cinnamic, and benzoic acids esters was tested on the pine weevil, Hylobius abietis (L.). Of 105 compounds screened for activity, 9 phenylpropanoates, 3 cinnamates, and 4 benzoates were found to be highly active antifeedants. To understand the structure-activity relationships of these compounds, a multivariate analysis study was performed. A number of molecular and substituent descriptors were calculated and correlated to results from two-choice feeding tests with H. abietis. Three local models were developed that had good internal predictive ability. External test sets showed moderate predictivity. In general, low polarity, small size, and high lipophilicity were characteristics for compounds having good antifeedant activity.
- Sunnerheim, Kerstin,Nordqvist, Anneli,Nordlander, Goeran,Borg-Karlson, Anna-Karin,Unelius, C. Rickard,Bohman, Bjoern,Nordenhem, Henrik,Hellqvist, Claes,Karlen, Anders
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p. 9365 - 9372
(2008/03/17)
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- A one-pot silyl-Reformatsky olefination
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A novel one-pot olefination reaction has been developed, involving the stereoselective formation of (E)-α,β-unsaturated esters/ketones from the reaction of α-bromocarbonyl compounds with aromatic aldehydes. The reactions use a reagent combination of trichlorosilane, and triethylamine and may proceed via the in situ formation of a trichlorosilyl ketene acetal. The general procedure offers key advantages (high conversions, low quantities of organic soluble by-products) over the conventional Wittig reaction.
- Smith, James M.,Greaney, Michael F.
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p. 8687 - 8690
(2008/03/14)
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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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- Wittig reactions in water media employing stabilized ylides with aldehydes. Synthesis of α,β-unsaturated esters from mixing aldehydes, α-bromoesters, and Ph3P in aqueous NaHCO3
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(Chemical Equation Presented) Water is demonstrated to be an effective medium for the Wittig reaction over a wide range of stabilized ylides and aldehydes. Despite sometimes poor solubility of the reactants, good chemical yields normally ranging from 80 to 98% and high E-selectivities (up to 99%) are achieved, and the rate of the reactions in water is unexpectedly accelerated. The efficiency of water as a medium in the Wittig reaction is compared to conventional organic solvents ranging from carbon tetrachloride to methanol. The aqueous Wittig reaction works best when large hydrophobic entities are present, such as aromatic, heterocyclic aromatic carboxaldehydes, and long-chain aliphatic aldehydes with triphenylphosphoranes. The E/Z-isomeric ratio of the Wittig products appears dependent on the electron-accepting/donating capacity and the location of the substituents present in the aromatic ring. The effect of additives, such as benzoic acid, LiCl, and sodium dodecyl sulfate (SDS), on the Wittig reaction has been explored. The Wittig reaction can also be conducted in the presence of acidic entities, such as phenols and carboxylic acids. In addition, large α-substituents in the aliphatic aldehydes do not jeopardize the reaction. It is also demonstrated that hydrates of aldehydes can be used directly in the aqueous Wittig reaction as substrates. The scope of the aqueous Wittig reaction is extended to 24 examples of one-pot mixtures of Ph3P, α-bromoesters, and aldehydes in sodium bicarbonate solution (at 20°C for 40 min to 3 h) to provide Wittig products of up to 99% yield and up to 98% E-selectivity. Since water is inexpensive, extremely easy to handle, and represents no environmental concerns, it should be considered a possible medium for new organic reactions.
- El-Batta, Amer,Jiang, Changchun,Zhao, Wen,Anness, Robert,Cooksy, Andrew L.,Bergdahl, Mikael
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p. 5244 - 5259
(2008/02/07)
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- NOVEL COMPOUNDS FOR MODULATING CELL PROLIFERATION
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Novel styrylacrylonitrile compounds which are useful in treating a variety of cell proliferative disorders such as cancer are disclosed.
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Page/Page column 89
(2008/06/13)
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- A microwave-accelerated esterification of α,β-unsaturated acids with alkyl or aryl carbonochloridate and triethylamine in acetonitrile as a novel esterifying reagent mixture
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An efficient synthesis of α,β-unsaturated esters by treatment of the corresponding acids with alkyl or aryl carbonochloridate, triethylamine, and acetonitrile was accomplished for the first time under microwave irradiation for 10 min. The esters 1b-24b were isolated in 71-97% yield.
- Pathania, Vinod,Sharma, Anuj,Sinha, Arun K.
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p. 811 - 816
(2007/10/03)
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- Water is an efficient medium for Wittig reactions employing stabilized ylides and aldehydes
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Water is demonstrated to be an excellent medium for the Wittig reaction employing stabilized ylides and aldehydes. Although the solubility in water appears to be an unimportant characteristic in achieving good chemical yields and E/Z-ratios, the rate of W
- Dambacher, Jesse,Zhao, Wen,El-Batta, Amer,Anness, Robert,Jiang, Changchun,Bergdahl, Mikael
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p. 4473 - 4477
(2007/10/03)
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- Very short and efficient syntheses of the spermine alkaloid kukoamine A and analogs using isolable succinimidyl cinnamates
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Direct selective acylation of the primary amino functions of spermine and spermidine with a variety of isolable succinimidyl cinnamates, followed by catalytic hydrogenation, gave high yields of the spermine alkaloid kukoamine A and analogs suitable for structure-activity relationship studies. Suitable succinimidyl cinnamates were readily obtained through Wittig reaction of aromatic aldehydes with the ylides Ph3P=CRCO2Me, followed by saponification and activation with N-hydroxysuccinimide in the presence of N,N'-dicyclohexylcarbodiimide. Copyright
- Garnelis, Thomas,Athanassopoulos, Constantinos M.,Papaioannou, Dionissios,Eggleston, Ian M.,Fairlamb, Alan H.
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p. 264 - 265
(2007/10/03)
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- BENZO-FUSED 5-MEMBERED HETROCYCLE COMPOUNDS,PROCESS FOR PREPARATION OF THE SAME, AND USE THEREOF
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A compound represented by the formula: (wherein, R1 and R2 are the same or different and each represents a hydrogen atom, hydrocarbon group or heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3-8 membered iso- or heterocyclic group, R3 represents a cyclic group, a hydroxy group, a mercapto group that may have oxo, or an amino group, R4 represents a hydrogen atom, a hydrocarbon group, a hydroxy group, a mercapto group which may have oxo, or an amino group, or R2 and R4 may link together to form a double bond, X represents a bond or a linear hydrocarbon group, W represents an oxygen atom or a sulfur atom, ring B represents a 5-8 membered nitrogen-containing heterocyclic group, ring C represents a benzene ring, and --- represents a single bond or a double bond), or a salt or a prodrug thereof that has excellent neurodegenerative inhibitory activity and brain penetrability, and is useful as an agent for preventing/treating neurodegenerative diseases.
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- New insights into the acid-promoted reaction of caffeic acid and its esters with nitrite: Decarboxylation drives chain nitrosation pathways toward novel oxime derivatives and oxidation/fragmentation products thereof
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In 0.05 M acetate buffer, pH 4, containing 1% methanol, caffeic acid (1a) (2 × 10-3 M) reacted smoothly with nitrite (NO2-) (4 × 10-3 M) to afford as main products the novel 2-hydroxy- and 2-methoxyaldoximes 7a,b, the 2-oxoaldoxime 9a, 3,4-dihydroxybenzoic acid, 3,4-dihydroxybenzaldehyde, and the known furoxan 3c and benzoxazinone 4b in smaller amounts. At lower 1a concentration (e.g., 1 × 10-4 M), 7a was the main product, whereas with 0.1 M 1a and 0.5 M NO2- 3c and 9a were prevailing. At pH 2, 7a was still the most abundant product, together with 3,4-dihydroxybenzaldehyde and some 9a, whereas at pH 1 9a and 3,4-dihydroxybenzaldehyde were formed in higher yields. No evidence for ring nitration products, including the previously reported 4,5-dihydroxy-2-nitrobenzaldehyde, was obtained. At 2 × 10-3 M concentration and at pH 4, caffeic acid methyl ester (1b) reacted with NO2- chiefly via ring nitration and/or dimerization to give 5a, the novel nitrated neolignan derivative 10, and the parent 6. Chlorogenic acid (1c) afforded only the ring nitrated derivative 5b. A unifying mechanism for the reaction of 1a and its esters with NO2- is proposed involving reversible formation of nitroso intermediates via chain nitrosation at the 2-position of the (E)-3-(3,4-dihydroxyphenyl)propenoic system. In the case of 1a, decarboxylation would drive the nitroso intermediates toward the formation of oximes 7a,b and 3c, reflecting nucleophilic addition of water, methanol, and NO2-, and their oxidation or breakdown products, viz. 9a, 3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, and the benzoxazinone 4b. In the case of esters 1b,c, to which decarboxylation is precluded, ring nitration or dimerization become the favored routes, triggered by preliminary oxidation at the catechol moiety.
- Napolitano, Alessandra,D'Ischia, Marco
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p. 803 - 810
(2007/10/03)
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- Syntheses of certain 3-aryl-2-propenoates and evaluation of their cytotoxicity
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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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- 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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- The total synthesis of salvianolic acid F
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An expeditious synthesis of salvianolic acid F 2 is described in 10% overall yield. Tetramethyl salvianolic acid F 3 was obtained in six steps in 39% overall yield and was converted into the target molecule using boron tribromide in 26% yield.
- Dalla, Vincent,Cotelle, Philippe
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p. 6923 - 6930
(2007/10/03)
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- Synthesis of cinnamaldehydes, esters of cinnamic acids and acylals of cinnamaldehydes by oxidation of arylpropenes with 2,3-dicyano-5,6- dichlorobenzoquinone (DDQ)
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1-Arylpropenes and 3-arylpropenes give cinnamaldehydes (yield= 80%) on oxidation with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in the presence of water. The conversion to aldehydes is promoted by electron-donating groups at the aromatic ring. On DDQ oxidation in the presence of methanol, methyl esters of cinnamic acids are the predominant products. DDQ oxidation of 1- or 3-(3,4-dimethoxyphenyl)-1-propene in the presence of acetic acid gives an acylal [the diacetate of (E)-3-(3,4-dimethoxyphenyl)-2-propene-1, 1-diol].
- Iliefski, Tommy,Li, Shiming,Lundquist, Knut
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p. 2413 - 2416
(2007/10/03)
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- An improved procedure for the epoxidation of methyl cinnamate derivatives and production of acid sensitive epoxides
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By using a biphasic epoxidation system, unreactive methyl cinnamate derivatives were epoxidized at higher rates, and epoxides that decomposed in the presence of m-chlorobenzoic acid (mCBA) to diol ester opening products under standard conditions were obtained in fair to excellent yields.
- Moyna, Guillermo,Williams, Howard J.,Scott
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p. 2235 - 2239
(2007/10/03)
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- A LUPANE TRITERPENE AND TWO TRITERPENE CAFFEATES FROM RHOIPTELEA CHILIANTHA
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A new lupane triterpene and two triterpene caffeates were isolated from the bark of Rhoiptelea chiliantha, together with two known triterpene acids.Their structures were elucidated on the basis of spectral and chemical evidence. - Keywords: Rhoiptelea chiliantha; Rhoipteleaceae; lupane triterpene; triterpene caffeate.
- Jiang, Zhi-Hong,Tanaka, Takashi,Kouno, Isao
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p. 1223 - 1226
(2007/10/02)
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