- Phenol compound ortho-position direct olefination method and olefinated phenol compound
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The invention relates to a phenol compound ortho-position direct olefination method and an olefinated phenol compound prepared with the method. The method comprises the steps that a phenol compound shown by the formula (II) and an olefin compound shown by
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Paragraph 0058; 0059; 0060; 0061
(2019/05/04)
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- Synthesis of 7-Azido-3-Formylcoumarin – A Key Precursor in Bioorthogonally Applicable Fluorogenic Dye Synthesis
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Coumarins represent an important group of natural products and a common part of various drugs and fluorescent dyestuffs. Herein, we present the synthesis of a coumarin that can serve as a key starting material in the design and synthesis of bioorthogonally applicable fluorogenic dyes. The synthesis of 7-azido-3-formylcoumarin started from 7-diallylaminocoumarin. This allyl protected aminocoumarin is otherwise hard to obtain by conventional methods but was conveniently accessed in good yields by a sequential, Wittig-reaction–UV isomerization process. This sequential approach was studied in more details and applied for the synthesis of a series of substituted coumarins even in one-pot.
- Pünk?sti, Zoltán,Kele, Péter,Herner, András
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supporting information
p. 1183 - 1188
(2018/03/21)
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- Microwave-Assisted Synthesis of Phenylpropanoids and Coumarins: Total Synthesis of Osthol
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Herein we describe a one-pot microwave-assisted method for the synthesis of cinnamic acid and coumarin derivatives. The synthesis begins with an aldehyde synthon, and the chosen reaction conditions determine whether a cinnamic acid or coumarin derivative is formed. A regioselective Claisen rearrangement was also efficiently incorporated into the synthetic sequence to further increase the complexity of the product. Notably, this approach provides high product yields and selectivities without the need of a phenol protecting group.
- Konrádová, Daniela,Kozubíková, Hana,Dole?al, Karel,Pospí?il, Ji?í
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p. 5204 - 5213
(2017/09/29)
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- Palladium nanoparticles immobilized on amphiphilic and hyperbranched polymer-functionalized magnetic nanoparticles: An efficient semi-heterogeneous catalyst for Heck reaction
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To address the obstacles facing the use of palladium-based homogeneous and heterogeneous catalysts in C─C cross-coupling reactions, a novel semi-heterogeneous support was developed based on hyperbranched poly(ethylene glycol)-block-poly(citric acid)-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@PCA-b-PEG). Because of the surface modification of the Fe3O4 nanoparticles with amphiphilic and hyperbranched polymers (PCA-b-PEG), these hybrid materials are not only soluble in a wide range of solvents (e.g. water, ethanol and dimethylformamide) but also are able to trap Pd2+ ions via complex formation of free carboxyl groups of the PCA dendrimer with metal ions. The reduction of trapped palladium ions in the dendritic shell of Fe3O4@PCA-b-PEG leads to immobilized palladium nanoparticles. The morphology and structural features of the catalyst were characterized using various microscopic and spectroscopic techniques. The catalyst was effectively used in the palladium-catalysed Mizoroki–Heck coupling reaction in water as a green solvent. In addition, the catalyst can be easily recovered from the reaction mixture by applying an external magnetic field and reused for more than ten consecutive cycles without much loss in activity, exhibiting an example of a sustainable and green methodology.
- Tabatabaei Rezaei, Seyed Jamal,Shamseddin, Azin,Ramazani, Ali,Mashhadi Malekzadeh, Asemeh,Azimzadeh Asiabi, Pegah
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- Intermediates for macrocyclic compounds
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The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R1, R2, R3, R4, R5, R6, n1, m, p Z1, Z2, and Z3 are as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.
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Page/Page column 33; Sheet 15
(2015/11/30)
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- Vitamin D3 analogues that contain modified A- and seco-B-rings as hedgehog pathway inhibitors
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The hedgehog (Hh) signaling pathway is a developmental signaling pathway that has been implicated as a target for anti-cancer drug development in a variety of human malignancies. Several natural and synthetic vitamin D-based seco-steroids have been identified as potent inhibitors of Hh signaling with chemotherapeutic potential. These include the previously characterized analogue 4, which contains the northern CD-ring/side chain region of vitamin D3 (VD3) linked to an aromatic A-ring mimic through an ester bond. To further explore structure-activity relationships for this class of VD3-based Hh pathway inhibitors, we have designed, synthesized and evaluated several series of compounds that modify the length, composition, and stereochemical orientation of the ester linker. These studies have identified compounds 54 and 55, which contain an amine linker and an aromatic A-ring incorporating a para-phenol, as new lead compounds with enhanced potency against the Hh pathway (IC50 values Combining double low line 0.40 and 0.32 μM, respectively).
- Deberardinis, Albert M.,Raccuia, Daniel S.,Thompson, Evrett N.,Maschinot, Chad A.,Hadden, M. Kyle
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p. 156 - 171
(2015/02/19)
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- 2-Hydroxy-substituted cinnamic acids and acetanilides are selective growth inhibitors of Mycobacterium tuberculosis
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Selective chemical hits are required for feeding the initial discovery phase of the anti-tuberculosis therapeutics pipeline. These chemical entities should ideally target novel mechanisms of action in order to tackle drug resistance in Mycobacterium tuberculosis. In this work, hydroxycinnamic acid and acetamidophenol skeleta were employed for assessing the effects of constitutional isomerism on in vitro anti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free ortho hydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 μM against M. tuberculosis H 37Rv and selectivity index higher than 30.
- Guzman, Juan D.,Mortazavi, Parisa N.,Munshi, Tulika,Evangelopoulos, Dimitrios,McHugh, Timothy D.,Gibbons, Simon,Malkinson, John,Bhakta, Sanjib
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supporting information
p. 47 - 50
(2014/01/06)
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- Ylide hydrolysis in tandem reactions: A highly Z/E-selective access to 3-alkylidene dihydrobenzofurans and related analogues
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An efficient synthetic approach to benzoheterocycles has been developed based on the hydrolysis of key ylide intermediates in a tandem reaction, upon which a variety of 3-alkylidene dihydrobenzofurans and related benzoheterocyclic products can be obtained
- Zhu, Jian-Bo,Wang, Peng,Liao, Saihu,Tang, Yong
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supporting information
p. 3054 - 3057
(2013/07/26)
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- Novel Insect-Repellent Coumarin Derivatives, Syntheses, and Methods of Use
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This invention relates to novel coumarin derivative, formulations comprising same, and to methods of making and using these compounds and formulations, which are useful as repellents against insects and/or pests. The compounds also prevent illness and disease caused by insect/pest-borne vectors, and provide safer, more effective alternatives to existing repellents.
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Page/Page column 31
(2013/02/28)
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- Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): Development of ulimorelin (TZP-101) from Hit to Clinic
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High-throughput screening of Tranzyme Phar-ma's proprietary macrocycle library using the aequorin Ca2+-bioluminescence assay against the human ghrelin receptor (GRLN) led to the discovery of novel agonists against this G-protein coupled receptor. Early hits such as 1 (Ki = 86 nM, EC50 = 134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization. While such macrocycles are not fully rule-of-five compliant, principally due to their molecular weight and clogP, optimization of their pharmacokinetic properties proved feasible largely through conformational rigidification. Extensive SAR led to the identification of 2 (Ki = 16 nM, EC50 = 29 nM), also known as ulimorelin or TZP-101, which has progressed to phase III human clinical trials for the treatment of postoperative ileus. X-ray structure and detailed NMR studies indicated a rigid peptidomimetic portion in 2 that is best defined as a nonideal type-I′ β-turn. Compound 2 is 24% orally bioavailable in both rats and monkeys. Despite its potency, in vitro and in gastric emptying studies, 2 did not induce growth hormone (GH) release in rats, thus demarcating the GH versus GI pharmacology of GRLN. (Figure presented)
- Hoveyda, Hamid R.,Marsault, Eric,Gagnon, René,Mathieu, Axel P.,Vézina, Martin,Landry, Annick,Wang, Zhigang,Benakli, Kamel,Beaubien, Sylvie,Saint-Louis, Carl,Brassard, Martin,Pinault, Jean-Fran?ois,Ouellet, Luc,Bhat, Shridhar,Ramaseshan, Mahesh,Peng, Xiaowen,Foucher, Laurence,Beauchemin, Sophie,Bhérer, Patrick,Veber, Daniel F.,Peterson, Mark L.,Fraser, Graeme L.
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supporting information; scheme or table
p. 8305 - 8320
(2012/01/15)
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- Synthesis of n-hydroxycinnamides capped with a naturally occurring moiety as inhibitors of histone deacetylase
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Histone deacetylase (HDAC) inhibitors are regarded as promising therapeutics for the treatment of cancer. All reported HDAC inhibitors contain three pharmacophoric features: a zinc-chelating group, a hydrophobic linker, and a hydrophobic cap for surface recognition. In this study we investigated the effectiveness of osthole, a hydrophobic Chinese herbal compound, as the surface recognition cap in hydroxamate-based compounds as inhibitors of HDAC. Nine novel osthole-based N-hydroxycinnamides were synthesized and screened for enzyme inhibition activity. Compounds 9d, 9e, 9g exhibited inhibitory activities (IC50=24.5, 20.0, 19.6 nm) against nuclear HDACs in HeLa cells comparable to that of suberoylanilide hydroxamic acid (SAHA; IC 50=24.5 nm), a potent inhibitor clinically used for the treatment of cutaneous T-cell lymphoma (CTCL). While compounds 9d and 9e showed SAHA-like activity towards HDAC1 and HDAC6, compound 9g was more selective for HDAC1. Compound 9d exhibited the best cellular effect, which was comparable to that of SAHA, of enhancing acetylation of either a-tubulin or histone H3. Molecular docking analysis showed that the osthole moiety of compound 9d may interact with the same hydrophobic surface pocket exploited by SAHA and it may be modified to provide class-specific selectivity. These results suggest that osthole is an effective hydrophobic cap when incorporated into N-hydroxycinnamide-derived HDAC inhibitors.
- Huang, Wei-Jan,Chen, Ching-Chow,Chao, Shi-We,Lee, Shoei-Sheng,Hsu, Fen-Lin,Lu, Yeh-Lin,Hung, Ming-Fang,Chang, Chung-I
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experimental part
p. 598 - 607
(2010/12/25)
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- Palladium-catalyzed tandem heck-lactonization from o-iodophenols and enoates: Synthesis of coumarins and the study of the mechanism by electrospray ionization mass spectrometry
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The tandem Heck-lactonization reaction between enoates Z-1a,b, E-1a, E-2a-d, Z-2e, 2f, and o-iodophenols (4a-f) was studied in the presence of substoichiometric amounts of Pd(OAc)2 or PdCl2, under experimental conditions favoring the cationic mechanism (conditions A, B, and C), leading to coumarins 5a-f and 6a-e. Moderate to excellent yields were obtained under aqueous conditions (conditions A and B). Using electrospray ionization for transferring ions directly from solution to the gas phase, and mass spectrometry for structural assignments, key cationic palladium intermediates have been successfully intercepted and structurally characterized for the first time for this type of reaction.
- Fernandes, Talita De A.,Gontijo Vaz, Boniek,Eberlin, Marcos N.,Da Silva, Alcides J. M.,Costa, Paulo R. R.
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scheme or table
p. 7085 - 7091
(2010/12/25)
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- Synergy effect of sodium acetate and glycosidically bound volatiles on the release of volatile compounds from the unscented cut flower (Delphinium elatum L. "Blue Bird")
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Many modern floricultural varieties have lost their scent during traditional breeding programs. The factors that result in the nonscent emission of some cut flowers remain unclear. The objective of this study was to investigate whether the nonscent emissi
- Yang, Ziyin,Endo, Sakura,Tanida, Aya,Kai, Kenji,Watanabe, Naoharu
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experimental part
p. 6396 - 6401
(2010/07/05)
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- Efficient synthetic approach to heterocycles possessing the 3,3-disubstituted-2,3-dihydrobenzofuran skeleton via diverse palladium-catalyzed tandem reactions
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Various palladium-catalyzed cascade reactions of O-alkylated 2-iodophenol were explored in order to synthesize novel dihydrobenzofurans. An efficient tandem cyclization/anion capture reaction was developed to yield 3,3-disubstituted-2,3-dihydrobenzofurans. A small library of these compounds was prepared with a parallel organic synthesizer. A multi-component version of this reaction involving 2-iodophenol, an alkylating agent and a nucleophile, provided the same products. The methoxycarbonyl-substituted heterocyclic ring was hydrolyzed to a free acid, which could be used for further transformations.
- Szlosek-Pinaud, Magali,Diaz, Philippe,Martinez, Jean,Lamaty, Frédéric
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p. 3340 - 3349
(2007/10/03)
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- Induction of phenolic compounds in two cultivars of cucumber by treatment of healthy and powdery mildew-infected plants with extracts of Reynoutria sachalinensis
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Accumulation of phenolic compounds (p-coumaric, caffeic, and ferulic acids and p-coumaric acid methyl ester) was followed in susceptible (Mustang) and tolerant (Flamingo) cucumber (Cucumis sativus) cultivars. The objective was to determine whether these compounds played a role in resistance against powdery mildew following a prophylactic treatment with Milsana (leaf extracts from the giant knot weed Reynoutria sachalinensis, polygonaceae). This treatment significantly reduced the incidence of powdery mildew in both cultivars. Phenolic compounds were extracted from leaves. In the hydrolyzed fraction containing phenolic aglycones, levels of p-coumaric, caffeic, and ferulic acids and of p-coumaric acid methyl ester increased in all treatments (with leaf extracts of R. Sachalinensis, powdery mildew, or both) except the control, one or two days after treatment. In the fraction containing free phenolics, from the tested compounds, only ferulic acid showed an increase in cv. Flamingo (tolerant), and was particularly evident following treatments. On the other hand, the amounts of hydroxycinnamic acids increased rapidly in the two cultivars following Milsana treatment, suggesting their role in disease reduction. All compounds showed antifungal activity when tested against common pathogens of cucumber (Botrytis cinerea, Pythium ultimum, and P. aphanidermatum), but in general methyl esters were more fungitoxic than their corresponding free acids. This study suggests that cucumber is able to release antifungal compounds that are instrumental in repressing powdery mildew infection. This response is seemingly independent from the level of genetic resistance associated with each cultivar.
- Daayf, Fouad,Ongena, Marc,Boulanger, Renald,El Hadrami, Ismail,Belanger, Richard R.
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p. 1579 - 1593
(2007/10/03)
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- Synthesis and biological activity of cinnamaldehydes as angiogenesis inhibitors
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A series of 2-hydroxycinnamaldehyde derivatives was synthesized for examing a structure-activity relationship for inhibition of angiogenesis. The anti-angiogenic effects of 2'-substituted cinnamaldehydes and related analogs were determined in a chick embryo chorioallantoic membrane assay system.
- Kwon, Byoung-Mog,Lee, Seung-Ho,Cho, Young-Kwon,Bok, Song-Hae,So, Seung-Ho,Youn, Mi-Ran,Chang, Soo-Ik
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p. 2473 - 2476
(2007/10/03)
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- Carboxylic Esters as Radical Leaving Groups: A New and Efficient Gas-phase Synthesis of Benzofurans
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Flash vacuum pyrolysis (FVP) of o-allyloxycinnamate esters gives benzofurans in high yield, via cyclisation of a phenoxyl radical and subsequent cleavage of the carboxylic ester function; coumarins are obtained by FVP of the corresponding phenols.
- Black, Michael,Cadogan, J. I. G.,Cartwright, Gary A.,McNab, Hamish,MacPherson, Andrew D.
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p. 959 - 960
(2007/10/02)
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- Aromatization of arene 1,2-oxides. 1,2-Oxides of methyl phenylacetate and methyl trans-cinnamate
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Substituent migration is observed only to a minor extent during aromatization of the 1,2-oxide of methyl phenylacetate to methyl (o-hydroxyphenyl)acetate; the major aromatization pathway does not involve substituent migration. Substituent migration is not observed during aromatization of the 1,2-oxide of methyl trans-cinnamate to methyl o-coumarate.
- Chao, Herbert S.-I.,Berchtold, Glenn A.
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p. 1191 - 1194
(2007/10/02)
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