- COMPOUND FOR INHIBITING PGE2/EP4 SIGNALING TRANSDUCTION INHIBITING, PREPARATION METHOD THEREFOR, AND MEDICAL USES THEREOF
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A compound of formula (I), a preparation method therefor, a pharmaceutical composition containing a derivative thereof, and the therapeutic uses thereof, especially inhibiting PGE2/EP4 signalling transduction and the uses thereof for treating cancer, acute or chronic pain, migraine, osteoarthritis, rheumatoid arthritis, gout, bursitis, ankylosing spondylitis, primary dysmenorrhea, tumour or arteriosclerosis.
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- Immunomodulator
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The invention discloses an immunomodulator, and particularly relates to compounds for inhibiting IL-17A and application of the compounds serving as the immunomodulator in preparation of drugs. The invention discloses an application of a compound shown as a formula I or a stereoisomer thereof in preparing medicines for inhibiting IL-17A, and provides a new choice for clinically screening and/or preparing medicines for treating diseases related to IL-17A activity.
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Paragraph 0178-0182
(2021/02/10)
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- Immunomodulator
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The invention discloses an immunomodulator, and particularly relates to a compound shown as a formula I, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Experiments prove that the compound has good IL-17A inhibitory activity, can be used for preparing an IL-17A inhibitor and drugs for preventing and/or treating IL-17A mediated diseases (such as inflammation, autoimmune diseases, infectious diseases, cancers and precancerous syndromes), and provides a new medical possibility for clinical treatment of diseases related to abnormal IL-17A activity.
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Paragraph 0200-0204
(2021/02/10)
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- Visible Light Induced Reduction and Pinacol Coupling of Aldehydes and Ketones Catalyzed by Core/Shell Quantum Dots
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We present an efficient and versatile visible light-driven methodology to transform aryl aldehydes and ketones chemoselectively either to alcohols or to pinacol products with CdSe/CdS core/shell quantum dots as photocatalysts. Thiophenols were used as proton and hydrogen atom donors and as hole traps for the excited quantum dots (QDs) in these reactions. The two products can be switched from one to the other simply by changing the amount of thiophenol in the reaction system. The core/shell QD catalysts are highly efficient with a turn over number (TON) larger than 4 × 104 and 4 × 105 for the reduction to alcohol and pinacol formation, respectively, and are very stable so that they can be recycled for at least 10 times in the reactions without significant loss of catalytic activity. The additional advantages of this method include good functional group tolerance, mild reaction conditions, the allowance of selectively reducing aldehydes in the presence of ketones, and easiness for large scale reactions. Reaction mechanisms were studied by quenching experiments and a radical capture experiment, and the reasons for the switchover of the reaction pathways upon the change of reaction conditions are provided.
- Xi, Zi-Wei,Yang, Lei,Wang, Dan-Yan,Feng, Chuan-Wei,Qin, Yufeng,Shen, Yong-Miao,Pu, Chaodan,Peng, Xiaogang
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p. 2474 - 2488
(2021/02/05)
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- Light-driven MPV-type reduction of aryl ketones/aldehydes to alcohols with isopropanol under mild conditions
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Alcohols are versatile structural motifs of pharmaceuticals, agrochemicals and fine chemicals. With respect to green chemistry, the development of more sustainable and cost-efficient processes for converting ketones/aldehydes to alcohols is highly desired. Herein, a direct light-driven strategy for reducing ketones/aldehydes to alcohols using isopropanol as the reducing agent and solvent, in the presence of t-BuOLi, under an air atmosphere at room temperature is developed. This operationally simple light-promoted Meerwein-Ponndorf-Verley (MPV) type reduction can be used to produce various benzylic alcohol derivatives as well as applied to bioactive molecules and PEEK model compounds, demonstrating its application potential.
- Cao, Dawei,Xia, Shumei,Pan, Pan,Zeng, Huiying,Li, Chao-Jun,Peng, Yong
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supporting information
p. 7539 - 7543
(2021/10/12)
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- Synthesis of Indole/Benzofuran-Containing Diarylmethanes through Palladium-Catalyzed Reaction of Indolylmethyl or Benzofuranylmethyl Acetates with Boronic Acids
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The palladium-catalyzed synthesis of indole/benzofurancontaining diarylmethanes starting from indolylmethyl or benzofuranylmethyl acetates with boronic acids has been investigated. The success of the reaction is influenced by the choice of precatalyst: with indolylmethyl acetates the reaction works well with [Pd(η3-C3H5)Cl]2/XPhos while with benzofuranylmethyl acetates Pd2(dba)3/XPhos is more efficient. The good to high yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2- and 3-substituted indoles and 2-benzo[b]furans. The methodology can be advantageously extended to the preparation of a key precursor of Zafirlukast.
- Arcadi, Antonio,Calcaterra, Andrea,Chiarini, Marco,Fabrizi, Giancarlo,Fochetti, Andrea,Goggiamani, Antonella,Iazzetti, Antonia,Marrone, Federico,Marsicano, Vincenzo,Serraiocco, Andrea
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supporting information
p. 741 - 753
(2021/11/26)
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- Palladium-catalyzed Tsuji-Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles
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The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd2(dba)3/dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(η3-C3H5)Cl]2/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the η3-(benzofuryl)methyl complex. The high to excellent yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2-substituted benzo[b]furans. This journal is
- Arcadi, Antonio,Fabrizi, Giancarlo,Fochetti, Andrea,Ghirga, Francesca,Goggiamani, Antonella,Iazzetti, Antonia,Marrone, Federico,Mazzoccanti, Giulia,Serraiocco, Andrea
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p. 909 - 917
(2021/01/20)
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- Bulky N-Heterocyclic-Carbene-Coordinated Palladium Catalysts for 1,2-Addition of Arylboron Compounds to Carbonyl Compounds
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The synthesis of primary, secondary, and tertiary alcohols by the 1,2-addition of arylboronic acids or boronates to carbonyl compounds, including unactivated ketones, using novel bulky yet flexible N-heterocyclic carbene (NHC)-coordinated 2,6-di(pentan-3-yl)aniline (IPent)-based cyclometallated palladium complexes (CYPs) as catalysts is reported. The PhS-IPent-CYP-catalyzed reactions are efficient at low catalyst loadings (0.02–0.3 mol% Pd), and the exceptional catalytic activity for 1,2-addition is attributed to the steric bulk of the NHC ligand. These reactions can yield a wide range of functionalized benzylic alcohols that are difficult to synthesize by classical protocols using highly active organomagnesium or lithium reagents.
- Okuda, Yuta,Nagaoka, Masahiro,Yamamoto, Tetsuya
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p. 6291 - 6300
(2020/11/30)
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- Nickel-Catalyzed Amination of α-Aryl Methyl Ethers
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α-Aryl amines are prevalent in pharmaceutically active compounds and natural products. Herein, we describe a Ni-catalyzed protocol for their synthesis from readily available α-aryl ethers. While α-aryl ethers have been used as electrophiles in Ni-catalyzed C-C bond formations, their use in C-heteroatom bond formation is much less prevalent. Preliminary mechanistic insight suggests that oxidative addition is facilitated by an anionic ligand and that reductive elimination is a reversible process.
- Patel, Purvish,Rousseaux, Sophie A. L.
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p. 492 - 496
(2020/03/13)
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- Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine
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Facile reduction of aryl halides with a combination of 5% Pd/C, B2(OH)4, and 4-methylmorpholine is reported. Aryl bromides, iodides, and chlorides were efficiently reduced. Aryl dihalides containing two different halogen atoms underwent selective reduction: I over Br and Cl, and Br over Cl. Beyond these, aryl triflates were efficiently reduced. This combination was broadly general, effectuating reductions of benzylic halides and ethers, alkenes, alkynes, aldehydes, and azides, as well as for N-Cbz deprotection. A cyano group was unaffected, but a nitro group and a ketone underwent reduction to a low extent. When B2(OD)4 was used for aryl halide reduction, a significant amount of deuteriation occurred. However, H atom incorporation competed and increased in slower reactions. 4-Methylmorpholine was identified as a possible source of H atoms in this, but a combination of only 4-methylmorpholine and Pd/C did not result in reduction. Hydrogen gas has been observed to form with this reagent combination. Experiments aimed at understanding the chemistry led to the proposal of a plausible mechanism and to the identification of N,N-bis(methyl-d3)pyridin-4-amine (DMAP-d6) and B2(OD)4 as an effective combination for full aromatic deuteriation. (Figure presented.).
- Korvinson, Kirill A.,Akula, Hari K.,Malinchak, Casina T.,Sebastian, Dellamol,Wei, Wei,Khandaker, Tashrique A.,Andrzejewska, Magdalena R.,Zajc, Barbara,Lakshman, Mahesh K.
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supporting information
p. 166 - 176
(2020/01/02)
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- Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
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We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
- Aleku, Godwin A.,Leys, David,Roberts, George W.
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p. 3927 - 3939
(2020/07/09)
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- Well-Defined N-Heterocyclic Carbene-Palladium Complexes as Efficient Catalysts for Domino Sonogashira Coupling/Cyclization Reaction and C-H bond Arylation of Benzothiazole
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Well-defined and air-stable PEPPSI (Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation) themed palladium bis-N-heterocyclic carbene complexes have been developed for the domino Sonogashira coupling/cyclization reaction of 2-iodophenol with a variety of terminal alkynes and C-H bond arylation of benzothiazole with aryl iodides. The PEPPSI themed palladium complexes, 2a and 2b were synthesized in good yields from the reaction of corresponding imidazolium salts with PdCl2 and K2CO3 in pyridine. The new air-stable palladium-NHC complexes were characterized by NMR spectroscopy, X-ray crystallography, elemental analysis, and mass spectroscopy studies. The PEPPSI themed palladium(II) bis-N-heterocyclic carbene complexes 2a and 2b exhibited excellent catalytic activities for domino Sonogashira coupling/cyclization reaction of 2-iodophenol with terminal alkynes yielding benzofuran derivatives. In addition, the palladium complexes, 2a and 2b successfully catalyzed the direct C-H bond arylation of benzothiazole with aryl iodides as coupling partners in presence of CuI as co-catalyst.
- Yadav, Seema,Singh, Ajeet,Mishra, Isha,Ray, Sriparna,Mobin, Shaikh M.,Dash, Chandrakanta
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- Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides
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New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX2). Use of a different halide on ZnX2 dictates the selectivity, wherein the NaH-ZnI2 system delivers alcohols and NaH-ZnCl2 gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH2)∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H?Zn?Cl)2 is the key species for the production of amines.
- Ong, Derek Yiren,Yen, Zhihao,Yoshii, Asami,Revillo Imbernon, Julia,Takita, Ryo,Chiba, Shunsuke
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supporting information
p. 4992 - 4997
(2019/03/13)
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- From Benzofurans to Indoles: Palladium-Catalyzed Reductive Ring-Opening and Closure via β-Phenoxide Elimination
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Benzofurans can undergo ring-opening by a palladium-catalyzed process resulting in C?O bond breaking. Benzofuran-tethered 2-iodoanilines give synthetically interesting 2-(3-indolylmethyl)phenols in an overall reductive process. Mechanistic studies suggest that this unusual reaction proceeds by carbopalladation of benzofuran giving a 3-palladated 2,3-dihydrobenzofuran intermediate, which then fragments by an uncommon trans-elimination of the phenoxide group β to the metal. In this transformation, N,N-diisopropylethylamine (DIPEA) acts as a base and as a reducing agent: it regenerates palladium(0) from palladium(II), thus allowing catalytic turnover. (Figure presented.).
- Perego, Luca A.,Wagschal, Simon,Grüber, Raymond,Fleurat-Lessard, Paul,El Ka?m, Laurent,Grimaud, Laurence
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p. 151 - 159
(2018/12/05)
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- Transition-metal-free base catalyzed intramolecular cyclization of 2-ynylphenols for efficient and facile synthesis of 2-substituted benzo[b]furans
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A transition-metal-free base catalyzed intramolecular cyclization of 2-ynylphenols was developed for the facile synthesis of 2-substituted benzo[b]furans. Various 2-aryl and 2-alkyl substituted benzo[b]furans can be obtained with good to excellent yields
- Liu, Yong,Lu, Tao,Tang, Wei-Fang,Gao, Jian
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p. 28637 - 28641
(2018/08/29)
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- Enantioselective α-Benzylation of Acyclic Esters Using π-Extended Electrophiles
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The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1-ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX-9065a.
- Schwarz, Kevin J.,Yang, Chao,Fyfe, James W. B.,Snaddon, Thomas N.
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supporting information
p. 12102 - 12105
(2018/09/11)
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- Radical Cation Cyclopropanations via Chromium Photooxidative Catalysis
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The chromium photocatalyzed cyclopropanation of diazo reagents with electron-rich alkenes is described. The transformation occurs under mild conditions and features specific distinctions from traditional diazo-based cyclopropanations (e.g., avoiding β-hydride elimination, chemoselectivity considerations, etc.). The reaction appears to work most effectively using chromium catalysis, and a number of decorated cyclopropanes can be accessed in generally good yields.
- Sarabia, Francisco J.,Ferreira, Eric M.
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supporting information
p. 2865 - 2868
(2017/06/07)
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- C- ARYL GLYCOSID DERIVATIVES, PHARMACEUTICAL COMPOSITION, PREPARATION PROCESS AND USES THEREOF
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This invention relates to a kind of C-aryl glycoside derivatives, its pharmaceutical compositions, preparation methods, and uses thereof. The preparation method comprises: method 1: in a solvent, deprotecting the acetyl protecting groups of compound 1-f in the presence of a base; method 2: 1) compound 2-g reacts with via Mitsunobu reaction; 2) deprotecting the acetyl protecting groups of compound 2-f obtained from step 1; method 3: 1) compound 2-g reacts with via nucleophilic substitution reaction; 2) deprotecting the acetyl protecting groups of compound 3-f obtained from step 1. The pharmaceutical composition comprises a kind of C-aryl glycoside derivatives; it's pharmaceutically acceptable salts and/or prodrugs thereof and excipient thereof. This invention further relates to a kind of C-aryl glycoside derivatives, it's pharmaceutically acceptable salts or pharmaceutical compositions thereof for the use in preparation of a SGLT inhibitor. The C-aryl glycoside derivatives of this invention provides a new direction for the study of SGLT inhibitors.
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- SNAr catalysis enhanced by an aromatic donor-acceptor interaction; Facile access to chlorinated polyfluoroarenes
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Selective catalytic SNAr reaction of polyfluoroaryl C-F bonds with chloride is shown. Stoichiometric TMSCl makes the reaction exergonic and allows catalysis, which involves ground state elevation of chloride, aromatic donor-acceptor interactions, and stabilization of the Meisenheimer complex. Traditional cross-coupling of the products is now possible and demonstrates the utility.
- Senaweera, Sameera,Weaver, Jimmie D.
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p. 7545 - 7548
(2017/07/12)
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- 2'-carbonyl-3-bromo-spiro[benzofuran-2,4'-oxazolidine] compounds and preparation method thereof
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The invention discloses 2'-carbonyl-3-bromo-spiro[benzofuran-2, 4'-oxazolidine] compounds and a preparation method thereof. The 2'-carbonyl-3-bromo-spiro[benzofuran-2,4'-oxazolidine] compounds are photoactive compounds shown in the structural formula II. The 2'-carbonyl-3-bromo-spiro[benzofuran-2,4'-oxazolidine] compounds are photoactive spiro compounds, photoactive chiral spiro compounds with multiple functional groups substituted, such as photoactive chiral spiro compounds with azido groups, hydroxyl groups, allyl groups and anisole groups substituted, can be obtained through substitution reactions of bromine atoms at site 3 under different reaction conditions. Therefore, different kinds of other photoactive chiral spiro compounds are prepared by using the substitution reactions of bromine atoms, the range of the compounds is enlarged, and the potential application value is great.
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Paragraph 0054; 0056-0058
(2017/08/02)
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- Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined Palladium N-Heterocyclic Carbene Complexes
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Well-defined palladium N-heterocyclic carbene (NHC) complexes were employed in the one-pot tandem Heck alkynylation/cyclization sequence for preparing biologically relevant benzofuran compounds under copper-free conditions in a time-efficient step-reduced
- Kumar, Anuj,Gangwar, Manoj Kumar,Prakasham,Mhatre, Darshan,Kalita, Alok Ch.,Ghosh, Prasenjit
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p. 2882 - 2893
(2016/04/05)
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- A Mild TEMPO-Catalyzed Aerobic Oxidative Conversion of Aldehydes into Nitriles
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An efficient method to prepare nitriles from aldehydes using hexamethyldisilazane (HMDS) as the nitrogen source has been developed. The reactions were performed with 2,2,6,6-tetramethylpiperidine l-oxyl (TEMPO) as the catalyst, NaNO2 or TBN as the co-catalyst, and molecular oxygen as the terminal oxidant under mild conditions. A variety of aromatic, heteroaromatic, aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.
- Fang, Chaojie,Li, Meichao,Hu, Xinquan,Mo, Weimin,Hu, Baoxiang,Sun, Nan,Jin, Liqun,Shen, Zhenlu
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p. 1157 - 1163
(2016/04/19)
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- Chromium-Catalyzed Asymmetric Dearomatization Addition Reactions of Halomethyl Heteroarenes
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The first asymmetric dearomatization addition reaction of halomethyl arenes including benzofuran and benzothiophene was enabled by chromium catalysis. A variety of aldehydes served as suitable electrophiles under mild reaction conditions. Molecular complexities are quickly increased in a highly diastereo- and enantioselective manner.
- Tian, Qingshan,Bai, Jing,Chen, Bin,Zhang, Guozhu
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supporting information
p. 1828 - 1831
(2016/05/19)
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- A systematic exploration of the effects of flexibility and basicity on sigma (σ) receptor binding in a series of substituted diamines
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The sigma-1 receptor (S1R) has attracted a great deal of attention as a prospective drug target due to its involvement in numerous neurological disorders and, more recently, for its therapeutic potential in neuropathic pain. As there was no crystal structure of this membrane-bound protein reported until 2016, ligand generation was driven by pharmacophore refinements to the general model suggested by Glennon and co-workers. The generalised S1R pharmacophore comprises a central region where a basic amino group is preferred, flanked by two hydrophobic groups. Guided by this pharmacophore, S1R ligands containing piperazines, piperazinones, and ethylenediamines have been developed. In the current work, we systematically deconstructed the piperazine core of a prototypic piperazine S1R ligand (vide infra) developed in our laboratories. Although we did not improve the affinity at the S1R compared to the lead, we identified several features important for affinity and selectivity. These included at least one basic nitrogen atom, conformational flexibility and, for S1R, a secondary or tertiary amine group proximal to the anisole. Furthermore, S2R selectivity can be tailored with functional group modifications of the N-atom proximal to the anisole.
- Conroy, Trent,Manohar, Madhura,Gong, Yu,Wilkinson, Shane M.,Webster, Michael,Lieberman, Brian P.,Banister, Samuel D.,Reekie, Tristan A.,Mach, Robert H.,Rendina, Louis M.,Kassiou, Michael
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supporting information
p. 9388 - 9405
(2016/10/13)
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- Access to nitriles from aldehydes mediated by an oxoammonium salt
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A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.
- Kelly, Christopher B.,Lambert, Kyle M.,Mercadante, Michael A.,Ovian, John M.,Bailey, William F.,Leadbeater, Nicholas E.
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p. 4241 - 4245
(2015/04/14)
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- Synthesis of Perfluoroalkyl-Substituted Vinylcyclopropanes by Way of Enhanced Neighboring Group Participation
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A simple, high yielding, two-step, one-pot protocol for the preparation of trifluoromethyl-substituted vinylcyclopropanes from α-CF3 homoallyl alcohols is disclosed. Destabilization of the cationic intermediate by the electron-withdrawing CF3 group greatly enhances neighboring group participation of the alkene, allowing ring closure to predominate. The reaction can be extended to the difluoromethyl and pentafluoroethyl group, enabling the preparation of a diverse array of fluoroalkyl-substituted vinylcyclopropanes. A diverse array of fluoroalkyl-substituted vinylcyclopropanes are prepared in a simple, high-yielding, two-step, one-pot protocol by means of cationic ring-closure.
- Kelly, Christopher B.,Mercadante, Michael A.,Carnaghan, Emma R.,Doherty, Matthew J.,Fager, Diana C.,Hauck, John J.,Macinnis, Allyson E.,Tilley, Leon J.,Leadbeater, Nicholas E.
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p. 4071 - 4076
(2015/06/30)
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- Synthesis and Insecticidal Activity of Spinosyns with C9- O -Benzyl Bioisosteres in Place of the 2′,3′,4′-Tri- O -methyl Rhamnose
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The spinosyns are fermentation-derived natural products active against a wide range of insect pests. They are structurally complex, consisting of two sugars (forosamine and rhamnose) coupled to a macrocyclic tetracycle. Removal of the rhamnose sugar results in a >100-fold reduction in insecticidal activity. C9-O-benzyl analogues of spinosyn D were synthesized to determine if the 2′,3′,4′-tri-O-methyl rhamnose moiety could be replaced with a simpler, synthetic bioisostere. Insecticidal activity was evaluated against larvae of Spodoptera exigua (beet armyworm) and Helicoverpa zea (corn earworm). Whereas most analogues were far less active than spinosyn D, a few of the C9-O-benzyl analogues, such as 4-CN, 4-Cl, 2-isopropyl, and 3,5-diOMe, were within 3-15 times the activity of spinosyn D for larvae of S. exigua and H. zea. Thus, although not yet quite as effective, synthetic bioisosteres can substitute for the naturally occurring 2′,3′,4′-tri-O-methyl rhamnose moiety.
- Oliver, M. Paige,Crouse, Gary D.,Demeter, David A.,Sparks, Thomas C.
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p. 5571 - 5577
(2015/06/25)
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- Synthesis of iboga-like isoquinuclidines: Dual opioid receptors agonists having antinociceptive properties
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Some novel iboga-analogues consisting of benzofuran moiety and dehydroisoquinuclidine ring connected by -CH2-, (CH2)2 and (CH2)3 linkers have been synthesized with the view to develop potential antinociceptive drugs. The compounds 14 and 21 showed binding at the μ-opioid receptor (MOR), while the compound 11a exhibited dual affinities at both MOR and κ-opioid receptor (KOR). MAP kinase activation indicated all three compounds have opioid agonistic properties. The presence of a double bond and endo-methylcarboxylate group in the dehydroisoquinuclidine ring and the benzofuran and methylene spacer appeared to be essential for opioid receptor binding. Further studies demonstrated 11a caused significant antinociception in mice in the hot-plate test which was comparable to that produced by morphine. The compound 11a was also found to be nontremorigenic unlike various iboga congeners. This study identifies a new pharmacophore which may lead to the development of suitable substitute of morphine in the treatment of pain.
- Banerjee, Tuhin Suvro,Paul, Sibasish,Sinha, Surajit,Das, Sumantra
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p. 6062 - 6070
(2015/02/02)
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- Palladium-catalyzed hydroxymethylation of aryl-and heteroarylboronic acids using aqueous formaldehyde
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Cyclometallated NHC palladium complexes prepared from palladium(II) acetate [Pd(OAc)2] and unsymmetrical 1,3-diarylimidazolinium salts catalyzed the hydroxymethylation of (hetero)arylboronic acids using an excess amount of formalin to afford (hetero)arylm
- Yamamoto, Tetsuya,Zhumagazin, Azamat,Furusawa, Takuma,Tanaka, Ryoji,Yamakawa, Tetsu,Oe, Yohei,Ohtab, Tetsuo
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supporting information
p. 3525 - 3529
(2015/01/09)
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- Synthesis and cytotoxic activity of novel hybrid compounds between 2-alkylbenzofuran and imidazole
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A series of novel hybrid compounds between 2-alkylbenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of 2-methyl-imidazole or 2-ethyl-imidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or methoxyphenacyl group were vital for modulating cytotoxic activity. In particular, hybrid compound 29 was found to be the most potent compound against five strains human tumor cell lines and more active than cisplatin (DDP), while hybrid compound 26 was more selective toward colon carcinoma (SW480) and breast carcinoma (MCF-7) with IC50 value 44.0- and 36.8-fold more sensitive to DDP.
- Wan, Wei-Chao,Chen, Wen,Liu, Lan-Xiang,Li, Yan,Yang, Li-Juan,Deng, Xiao-Yan,Zhang, Hong-Bin,Yang, Xiao-Dong
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p. 1599 - 1611
(2014/03/21)
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- Synthesis and biological activity of novel 1-((benzofuran-2-yl)methyl)- 1Htriazole derivatives
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A series of novel 1-((benzofuran-2-yl)methyl)-1H-triazole derivatives has been synthesized and tested in vitro against a panel of five different human tumor cell lines. The results show that the existence of benzotriazole or 1,2,3- triazole ring and substitution of the triazolyl-3-position with a naphthylacyl, 4-bromophenacyl or 4-methylbenzyl group could be crucial for promoting cytotoxic activity. Compounds 18, 19, 20 and 25 were found to have the most potent activities selectively against HL-60, SMMC-7721 and MCF-7 cell lines respectively. In particular, compound 20 was more selective towards HL-60 and A549 cell lines with IC50 values of 0.62 and 1.60 μM.
- Shi, Yi-Min,Yang, Li-Juan,Chen, Wen,Sun, Cheng-Jun,Xu, Xiao-Liang,Zhou, Shu-Ya,Zhang, Hong-Bin,Yang, Xiao-Dong
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p. 975 - 984
(2014/10/15)
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- Hydrogenations without hydrogen: Titania photocatalyzed reductions of maleimides and aldehydes
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A mild procedure for the reduction of electron-deficient alkenes and carbonyl compounds is described. UVA irradiations of substituted maleimides with dispersions of titania (Aeroxide P25) in methanol/acetonitrile (1:9) solvent under dry anoxic conditions led to hydrogenation and production of the corresponding succinimides. Aromatic and heteroaromatic aldehydes were reduced to primary alcohols in similar titania photocatalyzed reactions. A mechanism is proposed which involves two proton-coupled electron transfers to the substrates at the titania surface.
- Manley, David W.,Buzzetti, Luca,MacKessack-Leitch, Andrew,Walton, John C.
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p. 15324 - 15338
(2015/01/16)
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- Synthesis of 2-substituted benzofurans from o-iodophenols and terminal alkynes with a recyclable palladium catalyst supported on nano-sized carbon balls under copper- and ligand-free conditions
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We have developed a one-step synthesis of benzofurans from o-iodophenol and various terminal alkynes, by using Pd catalyst supported on nano-sized carbon balls (NCB) under copper- and ligand free conditions. This recyclable catalyst could be reused more than 5 times in the same heteroannulation reaction. The results have demonstrated that diverse 2-substituted benzofurans with tolerant functional groups can be prepared simply and conveniently under these conditions.
- Yum, Eul Kgun,Yang, Ok-Kyung,Kim, Ji-Eun,Park, Hee Jung
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p. 2645 - 2649
(2013/10/22)
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- A recyclable palladium-catalyzed synthesis of 2-methylene-2,3- dihydrobenzofuran-3-ols by cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols in ionic liquids
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A recyclable palladium-catalyzed synthesis of 2-methylene-2,3- dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl) phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relativelyn mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (5 equiv with respect to PdI2) and an organic base, such as morpholine (1 equiv with respect to 1), to give 2 in high yields (70%-86%). The PdI 2-KI catalytic system could be recycled up to six times without appreciable loss of activity. Moreover, products 2 could be easily converted in a one-pot fashion into 2-hydroxymethylbenzofurans 3 (52%-71%, based on 1) and 2-methoxymethylbenzofurans 4 (52%-80%, based on 1) by acid-catalyzed allylic isomerization or allylic nucleophilic substitution.
- Mancuso, Raffaella,Gabriele, Bartolo
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p. 10901 - 10911
(2013/10/22)
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- Domino sonogashira coupling/cyclization reaction catalyzed by copper and ppb levels of palladium: A concise route to indoles and benzo[b]furans
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Both indoles and benzo[b]furans can be obtained in high yield by the reactions of 2-iodoaniline derivatives and 2-iodophenols with terminal alkynes under mild conditions, namely in the presence of cuprous iodide (10-mol%) and a base in ethanol or 1,4-dioxane. Further investigation reveals that palladium contaminants as low as 100 ppb are responsible for these successful couplings. It is worth noting that simple aliphatic substituted terminal alkynes could be tolerated to smoothly produce indole and benzo[b]furan derivatives. Copyright
- Wang, Ruiping,Mo, Song,Lu, Yongzhong,Shen, Zengming
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supporting information; experimental part
p. 713 - 718
(2011/05/15)
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- A novel synthesis of 2-functionalized benzofurans by palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols followed by acid-catalyzed allylic isomerization or allylic nucleophilic substitution
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(Chemical Equation Presented) A novel two-step synthesis of 2-hydroxymethylbenzofurans 3 and 2-alkoxymethylbenzofurans 4-6, based on palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols 1 under basic conditions to give 2-methylene-2,3-dihydrobenzofuran-3-ols 2, followed by acid-catalyzed isomerization or allylic nucleophilic substitution with alcohols as nucleophiles, is reported. Cycloisomerization reactions leading to 2 (80-98% yields) were carried out at 40°C in MeOH as the solvent, in the presence of a base and catalytic amounts of PdX2 + 2KX (X = Cl, I). Isomerization reactions of 2 readily occurred at 25-60 °C in DME as the solvent, with H2SO4 as the proton source, to give 2-hydroxymethylbenzofurans 3 in 65-90% yields. In a similar manner, allylic nucleophilic substitution reactions of 2 with ROH as nucleophiles [carried out at 25-40°C in ROH (R = Me) or ROH-DME mixtures (R = Bu, Bn) in the presence of H2SO4] afforded 2-alkoxymethylbenzofurans 4, 5, and 6 (R = Me, Bu, and Bn, respectively), in 65-98% yields.
- Gabriele, Bartolo,Mancuso, Raffaella,Salerno, Giuseppe
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supporting information; experimental part
p. 7336 - 7341
(2009/04/18)
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- Traceless stereoinduction in the one-pot assembly of all three rings of hexahydrodibenzopyrans
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A one-pot method has been developed for the synthesis of all three rings of the hexahydrodibenzopyran ring system. This process involves a tandem sequence consisting of a benzannulation reaction of an alkenyl Fischer carbene complex and an alkyne followed by an elimination reaction that generates an o-quinone methide chromium tricarbonyl complex that is finally followed by an intramolecular heteroatom Diels-Alder cycloaddition. The stereoinduction for the overall process begins with the transfer of stereochemical information from the chiral center at the propargylic ether in the alkyne to the planar center of chirality in the in situ generated arene chromium tricarbonyl complexed intermediate and finally, after base-induced elimination to generate an o-quinone methide chromium tricarbonyl complexed intermediate, a transfer of chirality from the planar center of chirality in the o-quinone methide complex to the two new centers of chirality at positions 6a and 10a in the hexahydrodibenzopyran products upon intramolecular Diels-Alder reaction. The reactions of diastereomeric chiral propargyl ethers that contain an additional center of chirality can lead to high diastereoselectivity in the matched case and to low selectivity in the mismatched case. Copyright
- Korthals, Keith A.,Wulff, William D.
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p. 2898 - 2899
(2008/09/20)
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- Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation
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The synthesis of a novel series of aminostyrylbenzofuran derivatives 1a-w and their inhibitory activities for Aβ fibril formation were described. All the synthesized compounds were evaluated by thioflavin T (ThT) assay and displayed potent inhibitory activities for Aβ fibril formation. Among them, compounds 1i and 1q exhibited excellent inhibitory activities (IC50 = 0.07 and 0.08 μM, respectively) than those of Curcumin (IC50 = 0.80 μM) and IMSB (IC50 = 8.00 μM) as reference compounds. Both compounds were selected as promising candidates for further biological evaluation.
- Byun, Ji Hun,Kim, HyeYun,Kim, YoungSoo,Mook-Jung, Inhee,Kim, Dong Jin,Lee, Won Koo,Yoo, Kyung Ho
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scheme or table
p. 5591 - 5593
(2009/06/18)
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- PIPERIDINONES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, m and n have meanings given in the description, and pharmaceutically acceptable derivatives thereof, which compounds are useful in the treatment of diseases and conditions associated with inflammation.
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Page/Page column 109
(2008/12/07)
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- 4'-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
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Provided are 4'-O substituted isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
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Page/Page column 68
(2008/12/07)
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- Chemoenzymatic preparation of enantiopure l-benzofuranyl- and l-benzo[b]thiophenyl alanines
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Lipase mediated DKR followed by a chemical and an enzymatic hydrolytic step were combined for the synthesis of enantiopure l-benzofuranyl- and l-benzothienyl alanines.
- Podea, Paula Veronica,Tosa, Monica Ioana,Paizs, Csaba,Irimie, Florin Dan
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p. 500 - 511
(2008/09/19)
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- Syntheses and pyrolyses of benzofuran analogues of α-oxo-o- quinodimethane. A study on vinylcarbene-cyclopropene rearrangement
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(Chemical Equation Presented) Flash vacuum pyrolyses (FVP) of benzoic 3-methyl-2-benzofurancarboxylic anhydride (12) and benzoic 2-methyl-3- benzofurancarboxylic anhydride (13) at 550°C and ca. 10-2 torr both give methylenebenzocyclobutenone (21) as the major product and indenone (22) as the minor one. A mechanism involving generation of α-oxo-o- quinodimethane 11 as the primary pyrolysis product from FVP of 13, followed by elimination of a CO molecule to give carbene 24, which undergoes a vinylcarbene-cyclopropene rearrangement and a ring contraction of the resulting carbene 23, is proposed to account for the observed results. The proposed mechanism is further supported by a deuterium-labeling study on FVP of (2-benzofuryl)methyl-α,α-d2 benzoate (28-d2).
- Tseng, Pen-Wen,Yeh, Su-Wen,Chou, Chin-Hsing
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p. 3481 - 3485
(2008/09/21)
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- A study of the Claisen-Eschenmoser reaction for hydroxymethylbenzofurans and-indoles
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N,N-Dimethylacetamide dimethyl acetal reacted with 5(7)-substituted 2-(hydroxy-methyl)benzofurans to give N,N-dimethyl-2-(2-methylbenzofuran-3-yl) acetamides. Analogous reactions with 3-(hydroxymethyl)indole and 1-hydroxy-6-methyl-1,2,3,4-tetrahydro-carbazole afforded N,N-dimethyl-3-(3- indolyl)propionamide and N, N-dimethyl-2-(6-methyl-1,2,3,4-tetrahydrocarbazol-1- yl)acetamide, respectively.
- Mukhanova,Kukushkin,Ivanov,Alekseeva,Granik
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p. 325 - 329
(2008/02/13)
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- The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia-lyase from parsley
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Acrylic acids and alanines substituted with heteroaryl groups at the β-position were synthesized and spectroscopically characterized (UV, HRMS, 1H NMR, and 13C NMR spectroscopy). The heteroaryl groups were furanyl, thiophenyl, benzofuranyl, and benzothiophenyl and contained the alanyl side chains either at the 2- or 3-positions. While the former are good substrates for phenylalanine ammonia lyase (PAL), the latter compounds are inhibitors. Exceptions are thiophen-3-yl-alanine, a moderate substrate and furan-3-yl-alanine, which is inert. Possible reasons for these exceptions are discussed. Starting from racemic het eroaryl-2-alanines their D-enantiomers were prepared by using a stereodestructive procedure. From the heteroaryl-2- acrylates, the L-enantiomers of the heteroaryl-2-alanines were prepared at high ammonia concentration. These results can be best explained by a Friedel - Crafts-type electrophilic attack at the aromatic part of the substrates as the initial step of the PAL reaction.
- Paizs, Csaba,Katona, Adrian,Retey, Janos
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p. 2739 - 2744
(2008/02/03)
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- A new structural alternative in benzo[b]furans for antimicrobial activity
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Two series of 2-substituted and three new diacetyl benzofurans were synthesized through palladium-catalyzed reactions and their in vitro antimicrobial spectra were assessed. The compounds demonstrated mild to significant growth inhibition against antibiotic-susceptible standard and clinically isolated strains of Gram-positive and Gram-negative bacteria as well as human fungal pathogens. Ampicillin and kanamycin were used as references for antibacterial screening; nystatin and amphotericin B were used for antifungal screening. Varying substitution at the benzofuran moiety and subsequent antimicrobial screening identified the C-3-acetyl functionality as a new structural alternative for optimal antimicrobial property in the benzofuran class of compounds.
- Khan, M. Wahab,Alam, M. Jahangir,Rashid,Chowdhury
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p. 4796 - 4805
(2007/10/03)
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- Palladium-catalyzed cyclization reactions of propargylic carbonates with nucleophiles: A methodology for the syntheses of substituted 2,3-dihydrofurans and benzofurans
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Phenoxy-substituted 2,3-dihydrofurans were synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-pentyn-1-ol with phenols. The propargylic carbonate containing a nucleophilic phenoxy group also reacted in the presence of palladium to p
- Yoshida, Masahiro,Morishita, Yukio,Fujita, Mika,Ihara, Masataka
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p. 4381 - 4393
(2007/10/03)
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- Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b] furans in water
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An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh3, CuI and prolinol. This method can t
- Pal, Manojit,Subramanian, Venkataraman,Yeleswarapu, Koteswar Rao
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p. 8221 - 8225
(2007/10/03)
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- Novel cyclic amide derivatives
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Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH2—, —CO—, —O—, —CH(OR7)— or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.
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- BENZOFURAN DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
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Benzofuran derivatives represented by formula (I) or salts thereof: (wherein R1 represents a phenyl group or a hydrogen atom; k is 0 or 1; each of m, n, o, p, and q is an integer of 0 to 5; and each of R2 and R3 represents
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- Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
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Compounds of the general formula (I): wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT2receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2creceptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders.
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