- A SECOIRIDOID GLUCOSIDE FROM FRAXINUS FORMOSANA
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A new secoiridoid glucoside, fraxiformoside, was isolated from Fraxinus formosana, together with the known secoiridoid glucosides, ligstroside and isoligustroside.The structural elucidation of fraxiformoside by spectroscopic and chemical studies is described.Key Word Index - Fraxinus formosana; Oleaceae; leaves; secoiridoid glucosides; fraxiformoside; ligstroside; isoligustroside.
- Tanahashi, Takao,Watanabe, Hiroko,Itoh, Atsuko,Nagakura, Naotaka,Inoue, Kenichiro,et al.
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Read Online
- Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
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Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
- Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
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supporting information
p. 838 - 847
(2021/02/09)
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- Biotransformation of pungent constituents from ginger (Zingiber officinale Roscoe) by Colletotrichum gloeosporioides yields oxidative ortho–ortho coupling products
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This work investigated the biotransformation of ginger constituents (zingerone, [6]-shogaol, [6]-gingerol, and methyl-[6]-gingerol) by the pathogenic fungus Colletotrichum gloeosporioides. Experiments were carried out with and without deuterium-labelled compounds. The product metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and liquid chromatography solid phase extraction-nuclear magnetic resonance. Substrates supplied to the fungus were incorporated into metabolic pathways mostly by oxidation reactions, including aromatic carbon–carbon coupling. Zingerone and [6]-gingerol biotransformation products included biphenol dimers. A biodegradation pathway for biphenol formation was proposed based on the presence of the intermediate 4-(2-hydroxyethyl)-2-methoxyphenol, commonly identified from [6]-gingerol and [6]-shogaol biodegradation. This intermediate likely originates from a Baeyer–Villiger reaction followed by hydrolysis. The C–C coupling of molecules could result in phenolic oxidative ortho–ortho coupling, suggesting that biphenol dimers are products of C. gloeosporioides laccase catalysis.
- de ávila, Roberta Marques Dias,Toffano, Leonardo,Fernandes, Jo?o Batista,da Silva, Maria Fátima das Gra?as Fernandes,de Sousa, Lorena Ramos Freitas,Vieira, Paulo Cezar
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- Discovery of novel 2,3,5-trisubstituted pyridine analogs as potent inhibitors of IL-1β via modulation of the p38 MAPK signaling pathway
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Interleukin-1β is a central mediator of innate immune responses and inflammation. It plays a key role in a wide variety of pathologies, ranging from autoinflammatory diseases to metabolic syndrome and malignant tumors. It is well established that its inhibition results in a rapid and sustained reduction in disease severity, underlining the importance of having a repertoire of drugs of this class. At present, there are only three interleukin-1β blockers approved in the clinic. All of them are biologics, requiring parenteral administration and resulting in expensive treatments. In an exercise to identify small molecule allosteric inhibitors of MAP kinases, we discovered a series of compounds that block IL-1β release produced as a consequence of a stimulus involved in triggering an inflammatory response. The present study reports the hit-to-lead optimization process that permitted the identification of the compound 13b (AIK3-305) an orally available, potent and selective inhibitor of IL-1β. Furthermore, the study also reports the results of an in vivo efficacy study of 13b in a LPS endotoxic shock model in male BALB/c mice, where IL-1β inhibition is monitored in different tissues.
- Campos, Pedro M.,Carrasco, Esther,Gomez-Gutierrez, Patricia,Messeguer, Angel,Perez, Juan J.,Vega, Miguel
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- An Aldehyde Responsive, Cleavable Linker for Glucose Responsive Insulins
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A glucose responsive insulin (GRI) that responds to changes in blood glucose concentrations has remained an elusive goal. Here we describe the development of glucose cleavable linkers based on hydrazone and thiazolidine structures. We developed linkers with low levels of spontaneous hydrolysis but increased level of hydrolysis with rising concentrations of glucose, which demonstrated their glucose responsiveness in vitro. Lipidated hydrazones and thiazolidines were conjugated to the LysB29 side-chain of HI by pH-controlled acylations providing GRIs with glucose responsiveness confirmed in vitro for thiazolidines. Clamp studies showed increased glucose infusion at hyperglycemic conditions for one GRI indicative of a true glucose response. The glucose responsive cleavable linker in these GRIs allow changes in glucose levels to drive the release of active insulin from a circulating depot. We have demonstrated an unprecedented, chemically responsive linker concept for biopharmaceuticals.
- Mannerstedt, Karin,Mishra, Narendra Kumar,Engholm, Ebbe,Lundh, Morten,Madsen, Charlotte S.,Pedersen, Philip J.,Le-Huu, Priska,Pedersen, S?ren L.,Buch-M?nson, Nina,Borgstr?m, Bj?rn,Brimert, Thomas,Fink, Lisbeth N.,Fosgerau, Keld,Vrang, Niels,Jensen, Knud J.
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supporting information
p. 3166 - 3176
(2021/01/21)
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- Efficient Synthesis of Phenylacetate and 2-Phenylethanol by Modular Cascade Biocatalysis
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The green and sustainable synthesis of chemicals from renewable feedstocks by a biotransformation approach has gained increasing attention in recent years. In this work, we developed enzymatic cascades to efficiently convert l-phenylalanine into 2-phenylethanol (2-PE) and phenylacetic acid (PAA), l-tyrosine into tyrosol (p-hydroxyphenylethanol, p-HPE) and p-hydroxyphenylacetic acid (p-HPAA). The enzymatic cascade was cast into an aromatic aldehyde formation module, followed by an aldehyde reduction module, or aldehyde oxidation module, to achieve one-pot biotransformation by using recombinant Escherichia coli. Biotransformation of 50 mM l-Phe produced 6.76 g/L PAA with more than 99 % conversion and 5.95 g/L of 2-PE with 97 % conversion. The bioconversion efficiencies of p-HPAA and p-HPE from l-Tyr reached to 88 and 94 %, respectively. In addition, m-fluoro-phenylalanine was further employed as an unnatural aromatic amino acid substrate to obtain m-fluoro-phenylacetic acid; '96 % conversion was achieved. Our results thus demonstrated high-yielding and potential industrial synthesis of above aromatic compounds by one-pot cascade biocatalysis.
- Mao, Zuoxi,Liu, Lijun,Zhang, Yang,Yuan, Jifeng
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p. 2676 - 2679
(2020/06/03)
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- Chemical constituents with antimicrobial and antioxidant activity from the aerial parts of Callistemon lanceolatus (Sm.) Sweet
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Callistemon lanceolatus (Sm.) Sweet grows all over the world and used to treat cough and bronchitis. The air-dried powder of the aerial parts was exhaustively extracted with methanol and the concentrated extract was adsorbed on silica gel for preparation
- Nazreen, Syed,Mahboob Alam, Mohammad,Hamid, Hinna,Ali, Mohammad,Sarwar Alam, Mohammad
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supporting information
p. 3275 - 3279
(2019/01/14)
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- Synthesis of high added value compounds through catalytic oxidation of 2-phenylethanol: A Kinetic study
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An effective procedure was developed to produce high-value added phenolic compounds through the conversion of 2-phenylethanol (2-PhEt) by using acid-activated clays KSF for the hydrogen peroxide. Owing to KSF's ability to catalyze a variety of complex oxi
- Ben Hmida, Rania,Frikha, Nourzed,Bouguerra Neji, Soumaya,Kit, Geoffrey,Medina, Francisco,Bouaziz, Mohamed
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p. 124 - 133
(2019/12/03)
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- Synthesis method of p-hydroxyphenylethanol
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The invention relates to the field of organic synthesis, and discloses a synthesis method of p-hydroxyphenylethanol, which comprises the following steps: (1) mixing methanol, sodium methoxide and a catalyst, and performing stirring; (2) adding 4-chlorophenethyl alcohol, and carrying out a heating reaction; (3) cooling to room temperature, carrying out filtering, and drying by distillation to obtain a 4-methoxyphenethyl alcohol crude product; (4) adding the crude product into a solvent, and performing stirring; (5) dropwise adding hydrobromic acid, carrying out heating reflux, and carrying outa heat preservation reaction until the reaction is finished; (6) cooling to 55-65 DEG C, slowly adding an alkaline solution, and adjusting the pH value to 6-7; and (7) cooling to 8-12 DEG C, stirringfor 0.5-1.5h, filtering the material to obtain a wet filter cake, adding a solvent, heating for dissolution, separating water, and carrying out recrystallizing, filtering, and spin-drying to obtain the final product. The product purity can reach 99% or more, the yield can reach 90% or more, and the whole synthesis process has the advantages of simple and mild reaction conditions, simple post-treatment, and low cost.
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Paragraph 0033-0037; 0041-0045; 0049-0052
(2020/07/21)
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- Synthesis method of p-hydroxyphenethyl alcohol
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The invention discloses a method for synthesizing p-hydroxyphenethyl alcohol from phenethyl alcohol as a raw material. The method comprises the steps as follows: firstly, phenethyl alcohol and acid anhydride are subjected to an esterification reaction to obtain phenethyl alcohol ester; then, phenethyl alcohol ester and acid anhydride are subjected to an electrophilic substitution reaction under the action of a catalyst and a catalyst promoter to obtain 4-acryl phenethyl alcohol ester; next, 4-acryl phenethyl alcohol ester and hydrogen peroxide are subjected to a Baeyer-Villiger oxidation reaction under the action of organic acid and an oxidation catalyst to obtain 4-acyloxy phenethyl alcohol ester; finally, the 4-acyloxy phenethyl alcohol ester is subjected to a hydrolysis reaction in alkaline water to obtain p-hydroxyphenethyl alcohol. The process for synthesizing p-hydroxyphenethyl alcohol has the advantages that raw materials are widely sourced, the yield is high, the process is concise, few three wastes are produced and industrialization is easy to realize.
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- A deprotection procedure using SO3H silica gel to remove non-silyl protecting groups
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Protecting groups are indispensable in organic synthesis and there is a great need for a variety of deprotection methods. Here, we investigated the scope of the application of a deprotection procedure using SO3H silica gel, which we have previously reported as a desilylation procedure. Under these conditions, -OMOM, -OSEM, -OTHP, and -OAc groups and dimethyl acetal were cleaved. Pivaloyloxy, benzyloxy and methoxy carbonyl groups remained intact and selective deprotection of TBS groups in the presence of other protecting groups was accomplished. We succeeded in cleaving an acetyl group on a secondary alcohol in a highly polar nortropine derivative. Our findings here provide another deprotection option and would be helpful in the synthesis of multifunctional compounds.
- Karaki, Fumika,Kuwada, Miki,Tajiri, Saki,Kanda, Misaki,Yanai, Mari,Kamimura, Mitsuhiro,Itoh, Kennosuke,Fujii, Hideaki
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p. 212 - 220
(2019/05/06)
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- CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUATERNARY AMMONIUM SALT STRUCTURE
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The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β2-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma.
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Paragraph 0238
(2019/11/11)
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- Dealkylation of Lignin to Phenol via Oxidation-Hydrogenation Strategy
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Lignin is a renewable and abundant aromatic polymer found in plants. We herein propose a "cutting tail" methodology to produce phenol from lignin, which is achieved by combining Ru/CeO2 catalyst and CuCl2 oxidant via an oxidation-hydrogenation route. Phenol was obtained from separated poplar lignin with 13 wt % yield. Even raw biomass, such as poplar, birch, pine, peanut, bamboo willow, and straw, could be converted into phenol in 1-33 mg per gram of biomass.
- Wang, Min,Liu, Meijiang,Li, Hongji,Zhao, Zhitong,Zhang, Xiaochen,Wang, Feng
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p. 6837 - 6843
(2018/06/25)
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- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
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Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
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p. 5852 - 5869
(2018/11/10)
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- Rhenium-Loaded TiO2: A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N-Methylation of Amines Using H2 and CO2
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Herein, we report a heterogeneous TiO2-supported Re catalyst (Re/TiO2) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N-methylation of amines, by using H2 and CO2. Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3-phenylpropionic acid methyl ester to afford 3-phenylpropanol (pH2 =5 MPa, =5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N-methylation of amines, and the N-alkylation of amines with carboxylic acids or esters.
- Toyao, Takashi,Siddiki,Morita, Yoshitsugu,Kamachi, Takashi,Touchy, Abeda S.,Onodera, Wataru,Kon, Kenichi,Furukawa, Shinya,Ariga, Hiroko,Asakura, Kiyotaka,Yoshizawa, Kazunari,Shimizu, Ken-Ichi
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supporting information
p. 14848 - 14859
(2017/10/27)
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- Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety
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A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2′-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2′-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC50?=?0.4?±?0.02 & 0.6?±?0.03?μM against Hela and DU-145 respectively).
- Xie, Jin,Yang, Fengzhi,Zhang, Man,Lam, Celine,Qiao, Yixue,Xiao, Jia,Zhang, Dongdong,Ge, Yuxuan,Fu, Lei,Xie, Dongsheng
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p. 131 - 134
(2016/12/27)
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- Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives
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Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.
- Fernandez-Pastor, Ignacio,Fernandez-Hernandez, Antonia,Rivas, Francisco,Martinez, Antonio,Garcia-Granados, Andres,Parra, Andres
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p. 1737 - 1745
(2016/08/02)
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- α-Amino Acid-Isosteric α-Amino Tetrazoles
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The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
- Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
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supporting information
p. 3009 - 3018
(2016/03/26)
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- TiCl4/Et3N-Mediated Condensation of Acetate and Formate Esters: Direct Access to β-Alkoxy- and β-Aryloxyacrylates
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A methodology to build (E)-β-alkoxy- and (E)-β-aryloxyacrylate moieties from acetate and formate esters promoted by the TiCl4/Et3N system is presented. The reaction is compatible with a broad range of structural skeletons and elapses through an unusual condensation pathway. Taking into account the obtained results, we propose a plausible mechanism involving a bimetallic titanium intermediate for this type of transformation.
- álvarez-Calero, José María,Jorge, Zacarías D.,Massanet, Guillermo M.
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supporting information
p. 6344 - 6347
(2016/12/23)
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- p-Tyrosol: a new synthetic method and new types of pharmacological activity
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A new method for the synthesis of p-tyrosol, i.e., 2-(4-hydroxyphenyl)ethanol, has been developed, which considerably simplified the process of preparation of this pharmaceutical substance. The method includes nitration of 2-phenylethanol, catalytic hydrogenation of 2-(4nitrophenyl)ethyl nitrate, and nitrosation of 2-(4-aminophenyl)ethanol, followed by acid hydrolysis of the intermediate diazo compound. The method is easily feasible, furnishes the pharmaceutical substance of high quality, and is quite acceptable for commercialization. Antihypertensive and hemorheologic activities of p-tyrosol in spontaneously hypertensive rats were investigated per se and in combination with captopril. p-Tyrosol in the course administration with captopril was found to enhance the antihypertensive effect of the latter and eliminate its negative effect on red blood cell aggregation.
- Sysolyatin,Kryukov, Yu. A.,Malykhin,Muradov,Chernysheva,Aliev,Smol’yakova,Anishchenko,Sidekhmenova,Shamanaev, A. Yu.,Plotnikov
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p. 2210 - 2214
(2016/10/03)
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- Competing pathways in the photogeneration of didehydrotoluenes from (Trimethylsilylmethyl)aryl sulfonates and phosphates
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The scope of the photochemical generation of a,n-didehydrotoluene diradicals from aryl sulfonates and phosphates and their chemistry are explored. The thermally inaccessible a,2- and a,4-intermediates are efficiently obtained by irradiation of ortho- and para-(trimethylsilylme-thyl)phenyl triflates through heterolytic splitting of the ester anion from the substrate in the triplet state. Triplet phenyl cations are formed and the loss of trimethylsilyl cation from them affords the desired diradicals (3Me3SiCH2C6H4-OZ→ 3Me3SiCH2C6H4+→CH2C6H4). Triplet sensitization is required, for which acetone is used throughout. Direct irradiation leads, on the contrary, to photo-Fries fragmentation (1Me3SiCH2C6H4O-Z→Me3SiCH2C6H4O· + Z). With mesylates, where ester cleavage is less convenient, a further competition from the triplet is direct desilylation. Didehydrotoluenes are also obtained from the corresponding phosphates, although with poor efficiency.
- Crespi, Stefano,Ravelli, Davide,Protti, Stefano,Albini, Angelo,Fagnoni, Maurizio
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p. 17572 - 17578
(2015/02/18)
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- Reductive removal of methoxyacetyl protective group using sodium borohydride
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Herein, we have developed a mild and selective reductive deprotection method for the MAc protected alcohols using sodium borohydride. The new deprotection conditions provide a complete orthogonality between O-MAc and other protecting groups such as tert-butyl ester, N-Boc, Fmoc, Cbz, O-TBDMS, N-benzyl, O-benzyl, O-acetyl, N-acetyl, N-MAc, etc. In addition to O-MAc deprotection, this method is also applicable for S-MAc deprotection.
- Gadekar, Pradip K.,Hoermann, Maryann,Corbo, Faith,Sharma, Rajiv,Sarveswari,Roychowdhury, Abhijit
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p. 503 - 506
(2014/01/06)
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- Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme
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Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46. mM) and dopa (km 1.40. mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine.
- Torrens-Spence, Michael P.,Gillaspy, Glenda,Zhao, Bingyu,Harich, Kim,White, Robert H.,Li, Jianyong
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experimental part
p. 211 - 216
(2012/07/14)
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- Selective switchable iron-catalyzed hydrosilylation of carboxylic acids
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Selective reduction of carboxylic acids either to aldehydes or alcohols is achieved using a one pot procedure based on iron-catalyzed hydrosilylations. Using phenylsilane and (COD)Fe(CO)3 catalyst under UV-irradiation at rt, alcohols were obtained specifically in good yields, whereas aldehydes were selectively obtained using TMDS and (t-PBO)Fe(CO)3 catalyst under thermal activation.
- Misal Castro, Luis C.,Li, Haoquan,Sortais, Jean-Baptiste,Darcel, Christophe
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supporting information
p. 10514 - 10516,3
(2020/09/02)
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- Improving process conditions of hydroxytyrosol synthesis by toluene-4-monooxygenase
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Toluene-4-monooxygenase from Pseudomonas mendocina KR1 was recently engineered for the synthesis of hydroxytyrosol, a potent antioxidant. Following a 190-fold improvement in the enzyme activity by protein engineering means, improving the process conditions of this biocatalytic route was under taken for developing a liter-scale bioprocess. The growth stage was improved by selection of a rich media and harvesting the cells at the end of the logarithmic stage. The biotransformation stage was optimized by evaluating substrate concentration, cell density, and different operational modes. It was found that although reusing the cells in successive batch modes is feasible, their activity is dramatically decreased after the first use. In comparison, the activity of the cells following subsequent substrate addition in a fed batch mode was only slightly decreased. Furthermore, a better yield was obtained by extending the duration of the biotransformation stage, rather than adding more substrate. An overall concentration of 133 mg/L HTyr, corresponding to a volumetric productivity of 54 mg/L/h and a yield of 48% was achieved by a batch mode using 2 mM substrate. This is an order of magnitude improvement compared with the enzyme productivity before the process optimization. The use of beads conjugated with phenylboronic acid residues for adsorbing the product from the biotransformation bulk was evaluated. Though the recovery yield and purity were shown to be oppositely dependent, an average recovery procedure led to 2-fold purification of HTyr resulting in 84% purity with 70% recovery yield.
- Brouk, Moran,Fishman, Ayelet
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p. 121 - 127
(2012/11/07)
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- Iron-catalyzed hydrosilylation of esters
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The first hydrosilylation of esters catalyzed by a well defined iron complex has been developed. Esters are converted to the corresponding alcohols at 100 °C, under solvent-free conditions and visible light activation. Copyright
- Bezier, David,Venkanna, Gopaladasu T.,Castro, Luis C. Misal,Zheng, Jianxia,Roisnel, Thierry,Sortais, Jean-Baptiste,Darcel, Christophe
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supporting information; experimental part
p. 1879 - 1884
(2012/09/22)
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- TRICYCLIC COMPOUNDS, PREPARATION METHODS, AND THEIR USES
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease, and/or diabetic macular edema.
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Page/Page column 70
(2012/04/10)
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- Bioactive phenolic constituents from the seeds of Pharbitis nil
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Two new lignans, termed pharsyringaresinol (1) and pharbilignoside (2), a new phenylethanoid glycoside, termed pharbiniloside (3), and 22 known compounds, were isolated from the ethanol extract of the seeds of Pharbitis nil. The structures of the new compounds (1-3) were determined on the basis of spectroscopic analyses, including 2D-NMR and circular dichroism (CD) spectroscopy studies. Among the isolates, compounds 2, 11, 12, and 24 exhibited significant cytotoxicity against human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) with IC50 values ranging from 8.07 to 28.30 μM. In addition, compounds 11, 12 and 24 potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cells with IC50 values ranging from 14.7 to 19.9 μM.
- Kim, Ki Hyun,Ha, Sang Keun,Choi, Sang Un,Kim, Sun Yeou,Lee, Kang Ro
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experimental part
p. 1425 - 1429
(2012/01/06)
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- A mild and chemoselective method for the deprotection of tert-butyldimethylsilyl (TBDMS) ethers using iron(III) tosylate as a catalyst
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The most common method for the deprotection of TBDMS ethers utilizes stoichiometric amounts of tetrabutylammonium fluoride, n-Bu4N+F- (TBAF), which is highly corrosive and toxic. We have developed a mild and chemoselective method for the deprotection of TBDMS, TES, and TIPS ethers using iron(III) tosylate as a catalyst. Phenolic TBDMS ethers, TBDPS ethers and the BOC group are not affected under these conditions. Iron(III) tosylate is an inexpensive, commercially available, and non-corrosive reagent.
- Bothwell, Jason M.,Angeles, Veronica V.,Carolan, James P.,Olson, Margaret E.,Mohan, Ram S.
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supporting information; experimental part
p. 1056 - 1058
(2010/04/05)
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- The influence of key residues in the tunnel entrance and the active site on activity and selectivity of toluene-4-monooxygenase
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Site-directed saturation mutagenesis is a convenient method to fine tune enzyme activity and selectivity at known "hot spots". The objective of this work was to investigate the influence of mutations in the tunnel entrance of toluene 4-monooxygenase (T4MO
- Brouk, Moran,Derry, Netta-Lee,Shainsky, Janna,Zelas, Zohar Ben-Barak,Boyko, Yulia,Dabush, Keren,Fishman, Ayelet
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experimental part
p. 72 - 80
(2011/01/03)
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- Thermolysis of 4-(ω-hydroxyalkyl)-2,6-di-tert-butylphenols
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The process of thermolysis of tert-butylated hydroxyalkyl phenols includes de-tert-butylation, etherification, and fragmentation of the hydroxyalkyl group. On the basis of the proposed schemes of the mechanism of thermal de-tert-butylation the path of the search for catalysts for the synthesis of 4-hydroxyalkylphenols is defined and transformations of the by-products into biologically active substances were considered.
- Krysin,Egorova,Vasil'Ev
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body text
p. 275 - 283
(2010/07/15)
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- A simple and selective method for the O-AcCl removal using sodium borohydride
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A deprotection of chloroacetylated alcohols using NaBH4 is reported. The free alcohols are obtained in excellent yields. The reaction was performed on primary, secondary, alkyl, allyl, benzylic alcohols and phenols. The compatibility of the method with other sensitive or protective groups is demonstrated.
- Villedieu, Emmanuelle,Lopin-Bon, Chrystel,Berteina-Raboin, Sabine
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scheme or table
p. 2115 - 2118
(2010/06/14)
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- Oxidative burst inhibitory and cytotoxic amides and lignans from the stem bark of Fagara heitzii (Rutaceae)
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Two amides, heitziamide A and heitziamide B and two phenylethanoids, heitziethanoid A and heitziethanoid B together with thirteen known compounds were isolated from F. heitzii (Letouzey). The structures of all compounds were established by spectroscopic a
- Mbaze, Luc Meva'a,Lado, Jean Alexandre,Wansi, Jean Duplex,Shiao, Tze Chieh,Chiozem, David Dako,Mesaik, Muhammad Ahmed,Choudhary, Muhammad Iqbal,Lacaille-Dubois, Marie-Aleth,Wandji, Jean,Roy, Rene,Sewald, Norbert
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experimental part
p. 1442 - 1447
(2010/06/14)
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- An improved bouveault-blanc ester reduction with stabilized alkali metals
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Significantly improved Bouveault-Blanc conditions for ester reduction have been developed using sodium in silica gel (Na-SG), a free-flowing powder that can be easily handled in the open atmosphere. Primary alcohols were prepared in excellent yield from a variety of aliphatic esters under mild reaction conditions. The chemistry presented here is far safer than the classic Bouveault-Blanc reduction and is competitive with more modern hydride reduction methods.
- Bodnar, Brian S.,Vogt, Paul F.
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supporting information; experimental part
p. 2598 - 2600
(2009/08/07)
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- The chemoselective and efficient deprotection of silyl ethers using trimethylsilyl bromide
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An efficient and chemoselective cleavage of silyl ethers (primary, secondary and aromatic) by using catalytic quantities of trimethylsilyl bromide (TMSBr) in methanol is reported. A wide range of alkyl silyl ethers such as TBS, TIPS, and TBDPS can be chemoselectively cleaved in high yield in the presence of aryl silyl ethers. The deprotection of silyl esters was also achieved employing catalytic quantities of TMSBr. The Royal Society of Chemistry 2008.
- Shah, Syed Tasadaque A.,Guiry, Patrick J.
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experimental part
p. 2168 - 2172
(2009/02/01)
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- A convenient method to reduce hydroxyl-substituted aromatic carboxylic acid with NaBH4/Me2SO4/B(OMe)3
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The reduction of hydroxyl-substituted aromatic carboxylic acid with NaBH4/Me2SO4/B(OMe)3 is described. Borane is generated by the reaction of NaBH4 with Me2SO4 in THF, which is as efficient as the commercial one. B(OMe)3 has been successfully applied to increase the reactivity and selectivity of this reaction. The optimum ratio of borane/B(OMe)3/acid is studied, and a variety of hydroxyl-substituted aromatic acids are reduced in good yields.
- Zhou, Yuhan,Gao, Guchao,Li, Hui,Qu, Jingping
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p. 3260 - 3263
(2008/09/20)
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- Synthesis and biological activities of prenylated tyrosine derivatives, the metabolites of Pithomyces ellis
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2-[4-(2E)-3-Methylbut-2-enyloxy)phenyl]ethan-1-ol 3 and 3-[4-(2E)-3-methylbut-2-enyloxy) phenyl]-2-(acetylamino)propanoic acid 8 have been synthesized from 4-hydroxyphenylacetic acid 1, L-tyrosine 4, respectively, with an overall yield of 55% and 37%. The spectral data of synthetic 3 and 8 are in good agreement with those of natural 3 and 8, respectively. These synthetic 3 and 8 show significant brine shrimp lethality, but weak antioxidant and antibacterial activities.
- Venkateswarlu, Somepalli,Panchagnula, Gopala K.,Subbaraju, Gottumukkala V.
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p. 1063 - 1066
(2007/10/03)
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- Preparation and synthetic use of polymer-supported acetoacetate reagent
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Coumarin synthesis using polymer-supported acetoacetate reagent was carried out to produce various coumarin derivatives in excellent yield and purity with a facile work-up process. It was found that the polymer reagent could be recycled without any diminishment of the yield and purity. Georg Thieme Verlag Stuttgart.
- Hirai, Takeshi,Togo, Hideo
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p. 2664 - 2668
(2007/10/03)
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- New selective O-debenzylation of phenol with Mg/MeOH
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Carboxylate-benzyl and nitro-benzyl groups used in phenols protection were selectively debenzylated with 3-25 equiv of Mg in methanol at room temperature. Good yields of the desired phenols were obtained within 3-10 h from a wide variety of O-(carboxylate-benzyl)- or O-(nitro-benzyl)-phenols. Selective O-debenzylation was possible in the presence of O-(carboxylate-benzyl)- or O-(nitro-benzyl)-phenols with Mg/MeOH.
- Huang, Wei,Zhang, Xu,Liu, Hong,Shen, Jianhua,Jiang, Hualiang
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p. 5965 - 5967
(2007/10/03)
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- BiOClO4-mediated deprotection of silyl ethers
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TES- and TBS-protected alcohols undergo deprotection in good to excellent yield upon heating with 1equiv of BiOClO4-xH2O in CH 2Cl2. TBDPS- and TIPS-protected 2°alcohols are more resistant to deprotection. The use of this method for selective desilylation is, however, limited to the deprotection of alkyl silyl ethers in the presence of TBDPS-protected phenols.
- Crouch, R. David,Romany, Candice A.,Kreshock, Anna C.,Menconi, Karina A.,Zile, Jennifer L.
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p. 1279 - 1281
(2007/10/03)
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- Selective ortho-cleavage of methoxymethyl- and 4-methoxybenzyl ethers
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Iodine in methanol has been found to be an effective catalyst system for the cleavage of alkoxymethyl ethers. This catalyst system is particularly useful for the selective removal of ortho-methoxymethyl- and ortho-(4-methoxybenzyl) ethers in the presence
- Keith, John M.
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p. 2739 - 2742
(2007/10/03)
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- Process to extract phenolic compounds from a residual plant material using a hydrothermal treament
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The hydrothermal treatment is based on placing the crude residual plant material in contact with hot water in a closed reactor, comprising the following steps: a) placing the material to be treated in contact with water in a closed reactor, and adjusting the solid/liquid ratio so that it ranges from 1/5 to 1/15 (w/v): b) stirring; c) heating to a temperature between 180 and 240° C., and at a pressure so that the water is maintained in liquid phase; d) constantly stirring the mixture for a time period between 4 and 30 minutes; and e) cooling the reactor to approximately 40° C., unloading the mixture, filtering and recovering the liquid fraction.
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- SbCl5-wet acetonitrile: A new system for chemoselective O-desilylation
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A new efficient method for deprotection of TBDMS derivatives of phenols, primary alcohols, carboxylic acids and secondary amines, consisting of SbCl 5 and MeCN with 0.1% water (w/v), is reported. It effects inter alia desilylation of a CH2OTBDMS group in the presence of a ketal function.
- Glória, Paulo M. C.,Prabhakar, Sundaresan,Lobo, Ana M.,Gomes, Mário J. S.
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p. 8819 - 8821
(2007/10/03)
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- Probing crucial metabolic pathways in fungal pathogens of crucifers: Biotransformation of indole-3-acetaldoxime, 4-hydroxyphenylacetaldoxime, and their metabolites
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Indole-3-acetaldoxime is an intermediate of crucial importance in the biosynthesis of diverse plant secondary metabolites of Cruciferae. The metabolism of indole-3-acetaldoxime to indole-3-acetic acid via indole-3-acetonitrile by fungi that cause important plant diseases in crucifers, Leptosphaeria maculans (asexual stage Phoma lingam) causative agent of blackleg disease, Rhizoctonia solani causative agent of root rot disease, and Sclerotinia sclerotiorum causative agent of stem rot disease, is described. As well, the antifungal activity of indole-3-acetaldoxime and metabolites and the synthesis and biotransformation of 4-hydroxyphenylacetaldoxime by the same plant pathogens and by an insect fungal pathogen, Beauveria bassiana, are reported.
- Pedras, M. Soledade C.,Montaut, Sabine
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p. 3115 - 3120
(2007/10/03)
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- Simple, efficient, and selective deprotection of phenolic methoxymethyl ethers using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst
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A simple and efficient method has been developed for chemoselective deprotection of phenolic methoxymethyl (MOM) ethers using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst. The conversions occur at room temperature, and the yields of the deprotected phenols are excellent. The method is suitable for deprotection of phenolic MOM ethers of multifunctional bioactive natural products.
- Ramesh,Ravindranath,Das, Biswanath
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p. 7101 - 7103
(2007/10/03)
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- Compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
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The present invention relates to novel antidiabetic, hypolipidemic, antiobesity and hypocholesterolemic compounds of formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them.
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- 7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: A study on the importance of modifications at the side chain on the activity and solubility
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It was demonstrated in the early 1990s that adenosine exerts many physiological functions through the interaction with four different receptors, named A1, A2A, A2B, and A3. In the past few years, our group has been involved in the development of A2A antagonists, which led to the synthesis of SCH 58261 (1), the first potent and selective adenosine A2A antagonist, which has been widely used as a reference compound. In this paper, we present an extended series of pyrazolotriazolopyrimidines synthesized with the aim to investigate the influence of the substitutions on the pyrazole ring. The choice of the substituents was based on their capability to improve water solubility while retaining high affinity and selectivity at the human A2A adenosine receptor subtype. In this series, some structural characteristics that are important for activity, i.e., tricyclic structure, free amino group at 5-position, furan ring, and substituent at 7-position on the pyrazole moiety, have been maintained. We focused our attention on the nature of the phenyl ring substituent to improve water solubility. Following this strategy, we developed new compounds with good affinity and selectivity for A2A adenosine receptors, such as 8d (Ki 0.12 nM; hA1/hA2A ratio = 1025; Rm = 2.8), 8h (Ki 0.22; hA1/hA2A ratio = 9818; Rm = 3.4), 8i (Ki 0.18 nM; hA1/hA2A ratio = 994; Rm = 2.8), 8k (Ki 0.13 nM; hA1/hA2A ratio = 4430; Rm = 3.6), and 14b (Ki 0.19 nM; hA1/hA2A ratio = 2273; Rm = 2.7). All the new synthesized compounds have no significant interaction with either A2B or A3 receptor subtypes. This new series of compounds deeply enlightens some structural requirements to display high affinity and selectivity for the A2A adenosine receptor subtype, although our goal of identifying new compounds with increased water solubility was not completely achieved. On this basis, other strategies will be devised to improve this class of compounds with a profile that appears to be promising for treatment of neurodegenerative disorders, such as Parkinson's disease.
- Baraldi,Cacciari,Romagnoli,Spalluto,Monopoli,Ongini,Varani,Borea
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p. 115 - 126
(2007/10/03)
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- Selective formylation of alcohols in the presence of phenols with chloral
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Primary and secondary alcohols were formylated selectively in the presence of phenols by stirring with chloral in acetone over anhydrous K2CO3 at ambient temperatures in high yields.
- Ram, Ram N,Meher, Nabin Kumar
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p. 2997 - 3001
(2007/10/03)
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- A new vinyl ether type linker for solid-phase synthesis
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A new vinyl ether type of linker based on 4.-hydroxy phenethyl alcohol is developed for the solid-phase synthesis as demonstrated in the Suzuki type of aryl-aryl coupling reaction for the preparation of various biphenyl tetrazole derivatives. (C) 2000 Elsevier Science Ltd.
- Yoo,Gong,Choi,Seo,Kyu Yang Yi
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p. 6415 - 6418
(2007/10/03)
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- Synthesis of 13C-labeled possible intermediates in the biosynthesis of phenylethanoid derivatives, cornoside and rengyosides
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In order to clarify the biosynthetic pathway of C6-C2 unit compounds containing salidroside, cornoside, and rengyosides A and B in oleaceous plants, 13C-labeled putative precursors, 4-hydroxyphenylethanol, salidroside and cornoside, were prepared.
- Kuwajima, Hiroshi,Takai, Yoshitaka,Takaishi, Kiyokazu,Inoue, Kenichiro
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p. 581 - 586
(2007/10/03)
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