- Alpha-carbonyl alkenyl ester compound as well as preparation method and application thereof
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The invention provides an alpha-carbonyl alkenyl ester compound and a preparation method thereof. The alpha-carbonyl alkenyl ester compound is also used for reacting with primary or secondary amine to prepare an amide compound. Two steps of reactions are combined to develop an amido bond and peptide bond forming method which takes carboxylic acid and amine as starting raw materials and allene ketone as a condensing agent. Meanwhile, the alpha-carbonyl alkenyl ester compound of the alpha-amino acid is used as a polypeptide synthesis building block for solid-phase synthesis of polypeptide. The method is mild in reaction condition, simple to operate and high in yield. Compared with an existing amido bond condensation reagent, allene ketone has the advantages of being easy and convenient to prepare, good in stability, small in molecular weight and free of racemization when alpha-chiral carboxylic acid is activated and the like. The compound is a novel amido bond and peptide bond condensation reagent.
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Paragraph 0450-0455
(2021/08/25)
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- Ethyl 2-Cyano-2-(2-nitrobenzenesulfonyloxyimino) Acetate (ortho-NosylOXY)-Mediated Double Beckmann Rearrangement of Ketoximes under Microwave Irradiation: A Mechanistic Perception
-
A method for Beckmann rearrangement using ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino) acetate (o-NosylOXY) under microwave irradiation is reported. Ketoximes (19 examples) are converted to the corresponding amides/lactams with 69–97% yields in ~10 minutes without any Lewis acid or co-catalyst. This is an example of halogen-free organocatalytic Beckmann rearrangement. Nuclear magnetic resonance (NMR)- and high-resolution mass spectrometry (HRMS)-based detailed mechanistic investigation suggest that o-NosylOXY acts as an initiator. Such initiators are reported before based on density functional theory (DFT) calculations. However, we report here the HRMS signatures of two transient intermediates, the nitrilium ion and the nitrilium ion's dimeric species. Rigorous NMR-based investigation of the reaction mechanism is performed. Our results indicate that the reported Beckmann rearrangement proceeds via two consecutive rearrangements. (Figure presented.).
- Dev, Dharm,Kalita, Tapasi,Mondal, Tanmay,Mandal, Bhubaneswar
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p. 1427 - 1435
(2021/01/04)
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- Volatiles from the Psychrotolerant Bacterium Chryseobacterium polytrichastri
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The flavobacterium Chryseobacterium polytrichastri was investigated for its volatile profile by use of a closed-loop stripping apparatus (CLSA) and subsequent GC-MS analysis. The analyses revealed a rich headspace extract with 71 identified compounds. Compound identification was based on a comparison to library mass spectra for known compounds and on a synthesis of authentic standards for unknowns. Important classes were phenylethyl amides and a series of corresponding imines and pyrroles.
- Lauterbach, Lukas,Dickschat, Jeroen S.
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p. 3608 - 3617
(2020/09/22)
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- Styrene sulfone NLRP3 inflammasome inhibitor, preparation method and application thereof
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The invention relates to the field of styrene sulfone compounds and NLRP3 inhibitors, and particularly provides a styrene sulfone NLRP3 inflammasome inhibitor, a preparation method and application thereof, wherein the inhibitor is represented by a formula (1), n is selected from 0 and 1, X is selected from N and O, R1 is selected from different electron withdrawing or electron donating substituents, and R2 is selected from different fat or aromatic substituents. According to the invention, it is verified that the compounds represented by the general formula have NLRP3 inhibitory activity.
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Paragraph 0053; 0156-0157
(2020/10/30)
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- New approach for induction of alkyl moiety to aliphatic amines by NaBH(OAc)3 with carboxylic acid
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We had found the novel N-alkylation method, which utilizes carboxylic acids as alkyl sources with sodium triacetoxyborohydride [NaBH(OAc)3]. Our methodology had been revealed to have some advantages over the reported similar procedures. Through
- Tamura, Satoru,Sugawara, Aoi,Sato, Erika,Sato, Fuka,Sato, Keigo,Kawano, Tomikazu
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supporting information
(2020/04/15)
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- N-acylcarbazole as a selective transamidation reagent
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N-acylation reaction offers an opportunity to develop an efficient synthesis of amide group-containing molecules. We found that N-acyl carbazoles showed remarkable selectivity in transamidation. Sterically less hindered primary amines are selectively acylated with N-acyl carbazoles without any additives. Various functional groups such as alcohol, phenol, indole, and aniline moieties are tolerated under mild conditions. The synthetic utility was displayed in one-pot synthesis of an N-acyl polyamine natural product. The terminal amines of spermidine were selectively benzoylated with N-benzoyl carbazole, followed by acetylation reaction accomplished the total synthesis in a highly efficient manner.
- Kang, Bubwoong,Kuse, Masaki,Okamura, Hironori,Sakai, Asumi,Satoh, Tetsuya,Shinada, Tetsuro,Yasuno, Yoko
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p. 993 - 999
(2020/09/22)
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- Characterization of arylalkylamine n-acyltransferase from tribolium castaneum: an investigation into a potential next-generation insecticide target
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The growing issue of insecticide resistance has meant the identification of novel insecticide targets has never been more important. Arylalkylamine N-acyltransferases (AANATs) have been suggested as a potential new target. These promiscuous enzymes are involved in the N-acylation of biogenic amines to form N-acylamides. In insects, this process is a key step in melanism, hardening of the cuticle, removal of biogenic amines, and in the biosynthesis of fatty acid amides. The unique nature of each AANAT isoform characterized indicates each organism accommodates an assembly of discrete AANATs relatively exclusive to that organism. This implies a high potential for selectivity in insecticide design, while also maintaining polypharmacology. Presented here is a thorough kinetic and structural analysis of AANAT found in one of the most common secondary pests of all plant commodities in the world, Tribolium castaneum. The enzyme, named TcAANAT0, catalyzes the formation of short-chain N-acylarylalkylamines, with short-chain acyl-CoAs (C2-C10), benzoyl-CoA, and succinyl-CoA functioning in the role of acyl donor. Recombinant TcAANAT0 was expressed and purified from E. coli and was used to investigate the kinetic and chemical mechanism of catalysis. The kinetic mechanism is an ordered sequential mechanism with the acyl-CoA binding first. pH-rate profiles and site-directed mutagenesis studies identified amino acids critical to catalysis, providing insights about the chemical mechanism of TcAANAT0. A crystal structure was obtained for TcAANAT0 bound to acetyl-CoA, revealing valuable information about its active site. This combination of kinetic analysis and crystallography alongside mutagenesis and sequence analysis shines light on some approaches possible for targeting TcAANAT0 and other AANATs for novel insecticide design.
- Anderson, Ryan L.,Chen, Yu,Gelis, Ioannis,Leahy, James W.,Lewandowski, Eric M.,Mccaskey, Angelica N.,Merkler, David J.,O'flynn, Brian G.,Prins, Karin Claire,Rios-Guzman, Nasha M.,Shepherd, Britney A.,Suarez, Gabriela
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p. 513 - 523
(2020/03/11)
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- Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement
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A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO2F2 gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.
- Gurjar, Jitendra,Fokin, Valery V.
-
supporting information
p. 10402 - 10405
(2020/07/25)
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- Hydrosilane-Promoted Facile Deprotection of tert-Butyl Groups in Esters, Ethers, Carbonates, and Carbamates
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Combination of PdCl2 with 1,1,3,3-tetramethyldisiloxane in the presence of activated carbon was found to be an effective catalyst system for the cleavage reaction of C?O bond of O?t-Bu moieties. The present catalytic reaction offers a practical method for the deprotection of tert-butyl esters, tert-butyl ethers, O-Boc, and N-Boc derivatives under mild conditions. The addition of activated carbon in the reaction mixture was proved to be crucial for not only sustaining the catalytic activity but also trapping the palladium species after the reaction. (Figure presented.).
- Ikeda, Takuya,Zhang, Zhenzhong,Motoyama, Yukihiro
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supporting information
p. 673 - 677
(2019/01/04)
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- Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids
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A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.
- Hejazifar, Mahtab,Pálv?lgyi, ádám Márk,Bitai, Jacqueline,Lanaridi, Olga,Bica-Schr?der, Katharina
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p. 1841 - 1851
(2019/10/11)
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- Organocatalytic Decarboxylation of Amino Acids as a Route to Bio-based Amines and Amides
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Amino acids obtained by fermentation or recovered from protein waste hydrolysates represent an excellent renewable resource for the production of bio-based chemicals. In an attempt to recycle both carbon and nitrogen, we report here on a chemocatalytic, metal-free approach for decarboxylation of amino acids, thereby providing a direct access to primary amines. In the presence of a carbonyl compound the amino acid is temporarily trapped into a Schiff base, from which the elimination of CO2 may proceed more easily. After evaluating different types of aldehydes and ketones on their activity at low catalyst loadings (≤5 mol%), isophorone was identified as powerful organocatalyst under mild conditions. After optimisation many amino acids with a neutral side chain were converted in 28–99 % yield in 2-propanol at 150 °C. When the reaction is performed in DMF, the amine is susceptible to N-formylation. This consecutive reaction is catalysed by the acidity of the amino acid reactant itself. In this way, many amino acids were efficiently transformed to the corresponding formamides in a one-pot catalytic system.
- Claes, Laurens,Janssen, Michiel,De Vos, Dirk E.
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p. 4297 - 4306
(2019/08/26)
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- Flow-based enzymatic synthesis of melatonin and other high value tryptamine derivatives: A five-minute intensified process
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To increase the uptake of biocatalytic processes by industry, it is essential to demonstrate the reliability of enzyme-based methodologies directly applied to the production of high value products. Here, a unique, efficient, and sustainable enzymatic platform for the multi-gram synthesis of melatonin, projected to generate around 1.5 billion U.S. dollars worldwide by 2021, and its analogues was developed. The system exploits the covalent immobilization of MsAcT (transferase from Mycobacterium smegmatis) onto agarose beads increasing the robustness and longevity of the immobilized biocatalyst. The fully-automated process deriving from the integration between biocatalysis and flow chemistry is designed to maximize the overall yields (58-92%) and reduce reaction times (5 min), overcoming the limitation often associated with bioprocesses and bridging the gap between lab scale and industrial production.
- Contente, Martina Letizia,Farris, Stefano,Tamborini, Lucia,Molinari, Francesco,Paradisi, Francesca
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supporting information
p. 3263 - 3266
(2019/06/24)
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- SO2F2-Activated Efficient Beckmann Rearrangement of Ketoximes for Accessing Amides and Lactams
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A novel, mild and practical protocol for the efficient activation of the Beckmann rearrangement utilizing the readily available and economical sulfuryl fluoride (SO2F2 gas) has been developed. The substrate scope of the operationally simple methodology has been demonstrated by 37 examples with good to nearly quantitative isolated yields (over 90 % yield in most cases) in a short time, including B(OH)2, COOH, NH2, and OH substituted substrates. A tentative mechanism was proposed involving formation and elimination of key intermediate, sulfonyl ester.
- Zhang, Guofu,Zhao, Yiyong,Xuan, Lidi,Ding, Chengrong
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supporting information
p. 4911 - 4915
(2019/07/31)
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- Ruthenium-Catalyzed Oxidative Amidation of Alkynes to Amides
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Complex CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with 4-picoline N-oxide and primary and secondary amines to afford the corresponding amides. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry. Stoichiometric studies reveal that the true catalysts of the processes are the vinylidene cations [CpRu(=C=CHR)(PPh3)2]+ which are oxidized to the Ru(η2-CO)-ketenes by the N-oxide. Finally, nucleophilic additions of primary and secondary amines to the free ketenes yield the corresponding amides.
- álvarez-Pérez, Andrea,Esteruelas, Miguel A.,Izquierdo, Susana,Varela, Jesús A.,Saá, Carlos
-
supporting information
p. 5346 - 5350
(2019/07/08)
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- Production preparation method of p-nitrophenylethylamine hydrochloride
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The invention provides a production preparation method of p-nitrophenylethylamine hydrochloride, belongs to the technical field of drug synthesis, and solves the problems that in the prior art the synthetic p-nitrophenylethylamine hydrochloride is low in conversion rate of and is not suitable for large-scale industrial production. Synthesis steps include 1) amino protection, to be more specific, using beta-phenylethylamine as a raw material for reacting with an acyl protecting agent in a solvent to obtain an intermediate 1; 2) nitrating reaction, to be more specific, adding dropwise the intermediate 1 prepared by the step 1) into concentrated sulfuric acid, maintaining reaction temperature at room temperature, slowly adding dropwise concentrated nitric acid, after the completion of the reaction, adding crushed ice, adding an alkaline solution to adjust the pH to alkaline, and filtering to obtain an intermediate 2; and 3) deprotection, to be more specific, adding dropwise hydrochloric acid into the intermediate 2 in a solvent to adjust the pH to acid, heating to reflux, cooling, and precipitating the product p-nitrophenylethylamine hydrochloride. The production preparation method ofthe p-nitrophenylethylamine hydrochloride has low cost and high product yield, and is suitable for large-scale industrial production.
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-
Paragraph 0061
(2018/03/23)
-
- Preparation method of glimepiride impurity
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The invention belongs to the technical field of medicinal chemistry and particularly relates to a preparation method of a glimepiride impurity. The preparation method comprises the following steps: dropwise adding acetic anhydride into a solution of 2-phenethylamine and an organic solvent with a low boiling point to be subjected to reaction to generate N-acetyl phenethylamine; dropwise adding chlorosulfonic acid into the N-acetyl phenethylamine at the temperature of lower than 20 DEG C to be subjected to chlorosulfonation reaction, and performing hydrolysis after the reaction is completed to remove excess chlorosulfonic acid; performing filtration and washing to obtain an impurity J benzenesulfonyl chloride; performing ammonolysis on the impurity J benzenesulfonyl chloride to obtain an impurity J benzene sulfonamide; in acetone, enabling the impurity J benzene sulfonamide to firstly react with a catalyst and then react with trans-p-methylcyclohexyl isocyanate to obtain an impurity J acetyl substance; enabling the impurity J acetyl substance and ethanol to be subjected to alcoholysis under the condition of the catalyst to generate an impurity J and ethyl acetate; and performing refining to obtain a high-purity impurity J. The purity of the glimepiride impurity J prepared by the method is high, the liquid phase content of the glimepiride impurity J is greater than 98.5%, the rawmaterials used in the method are easily available, the process parameters are controllable, and the reaction is mild.
- -
-
Paragraph 0037-0039; 0048-0050; 0059-0061
(2020/04/02)
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- Direct and Catalytic Amide Synthesis from Ketones via Transoximation and Beckmann Rearrangement under Mild Conditions
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The Br?nsted acid-catalyzed synthesis of secondary amides from ketones under mild conditions is described via transoximation and Beckmann rearrangement using O-protected oximes as more stable equivalents of explosive O-protected hydroxylamines. This methodology could be applied to highly rearrangement-selective amide synthesis from α-branched alkyl aryl ketones and performed on a 1-g scale. The presence of water is essential for this reaction, and its role was clarified by isotope-labeling experiments.
- Hyodo, Kengo,Hasegawa, Genna,Oishi, Naoki,Kuroda, Kazuma,Uchida, Kingo
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p. 13080 - 13087
(2018/11/02)
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- Protection of COOH and OH groups in acid, base and salt free reactions
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We report an iron-catalyzed general functional group protection method with inexpensive reagents. This environmentally benign process does not use acids or bases, and does not produce waste products. Further purification beyond filtration and evaporation is, in most cases, unnecessary. Free COOH and OH groups can be protected in a one-pot reaction.
- Zhu, Xiaotao,Qian, Bo,Wei, Rongbiao,Huang, Jian-Dong,Bao, Hongli
-
supporting information
p. 1444 - 1447
(2018/04/12)
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- Biocatalytic N-Acylation of Amines in Water Using an Acyltransferase from Mycobacterium smegmatis
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A straightforward one-step biocatalyzed synthesis of different N-acyl amides in water was accomplished using the versatile and chemoselective acyltransferase from Mycobacterium smegmatis (MsAcT). Acetylation of primary arylalkyl amines was achieved with a range of acetyl donors in biphasic systems within 1 hour and at room temperature. Vinyl acetate was the best donor which could be employed in the N-acetylation of a large range of primary amines in excellent yields (85–99%) after just 20 minutes. Other acyl donors (including formyl-, propionyl-, and butyryl-donors) were also efficiently employed in the biocatalytic N-acylation. Finally, the biocatalyst was tested in transamidation reactions using acetamide as acetyl donor in aqueous medium, reaching yields of 60–70%. This work expands the toolbox of preparative methods for the formation of N-acyl amides, describing a biocatalytic approach easy to accomplish under mild conditions in water. (Figure presented.).
- Contente, Martina Letizia,Pinto, Andrea,Molinari, Francesco,Paradisi, Francesca
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p. 4814 - 4819
(2018/11/10)
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- Preparation method of acetylene amide mediated thioacid amide and application of acetylene amide mediated thioacid amide in thiopeptide synthesis
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The invention discloses an acetylene amide mediated method for selectively synthesizing carbonyl thioesters and ordinary thioesters. The ordinary thioesters are further used for preparing amides and peptides, and the carbonyl thioesters are used for preparing thioamides and thiopeptides. An addition reaction is carried out between acetylene amide in m-xylene and thiocarboxylic acid to selectivelyobtain the carbonyl thioester and ordinary thioester of which the ratio is 3:1 under the condition of 40 DEG C below zero; the ordinary thioesters can carry out a combination reaction with amines to produce amides and peptides; and the carbonyl can carry out a combination reaction with the amines to produce thioamides and thiopeptides. The method disclosed by the invention is mild in reaction conditions, free of any metal catalyst, high in reaction speed, high in yield, simple in operation and wide in application range. With respect to chiral thiocarboxylic acid in a position alpha of carboxyl, when thioamide bonds or thiopeptide bonds are formed from the carbonyl thioesters or when amido bonds or peptide bonds are formed from the ordinary thioesters, any racemization phenomenon can be avoided.
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-
Paragraph 0055
(2018/09/21)
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- Manganese-Catalyzed Direct Conversion of Ester to Amide with Liberation of H2
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A simple and efficient Mn-catalyzed acylation of amines is achieved using both acyl and alkoxy functions of unactivated esters with the liberation of molecular hydrogen as a sole byproduct. The present protocol provides an atom-economical and sustainable route for the synthesis of amides from esters by employing an earth-abundant manganese salt and inexpensive phosphine-free tridentate ligand.
- Mondal, Akash,Subaramanian, Murugan,Nandakumar, Avanashiappan,Balaraman, Ekambaram
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supporting information
p. 3381 - 3384
(2018/06/11)
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- Beckmann rearrangement of ketoxime catalyzed by N-methyl-imidazolium hydrosulfate
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Beckmann rearrangement of ketoxime catalyzed by acidic ionic liquid-N-methyl-imidazolium hydrosulfate was studied. Rearrangement of benzophenone oxime gave the desirable product with 45% yield at 90 ?C. When co-catalyst P2O5 was added, the yield could be improved to 91%. The catalyst could be reused three cycles with the same efficiency. Finally, reactions of other ketoximes were also investigated.
- Hu, Hongyu,Cai, Xuting,Xu, Zhuying,Yan, Xiaoyang,Zhao, Shengxian
-
-
- Hypervalent Iodine-Mediated Beckmann Rearrangement of Ketoximes
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We developed a Beckmann rearrangement employing hypervalent iodine reagent under mild conditions. The reaction of ketoxime with hypervalent iodine afforded the corresponding ketone, but premixing of hypervalent iodine and a Lewis acid was effective for promoting Beckmann rearrangement. Aromatic and aliphatic ketoximes were converted into their corresponding amides in good to high yields.
- Oishi, Ryohei,Segi, Kazutoshi,Hamamoto, Hiromi,Nakamura, Akira,Maegawa, Tomohiro,Miki, Yasuyoshi
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supporting information
p. 1465 - 1468
(2018/05/03)
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- Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines
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A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).
- Li, Hao,Tian, Ping,Xu, Jian-He,Zheng, Gao-Wei
-
supporting information
p. 3151 - 3154
(2017/06/23)
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- Convergent Total Synthesis of (±)-Apomorphine via Benzyne Chemistry: Insights into the Mechanisms Involved in the Key Step
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Convergent total synthesis of (±)-apomorphine hydrochloride was accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2]-cycloaddition reaction followed by a hydrogen migration. Through this sequence of transformations, the desired aporphine core was obtained regioselectively in 75% isolated yield. Since only one regioisomer was produced in the key step of the synthesis, a polar [4+2]-cycloaddition mechanism was proposed. Furthermore, NMR experiments and theoretical calculations were carried out to elucidate the hydrogen migration mechanism. (±)-Apomorphine hydrochloride was achieved after 9 steps in an overall yield of 8% involving benzyne chemistry.
- Muraca, Ana Carolina A.,Perecim, Givago P.,Rodrigues, Alessandro,Raminelli, Cristiano
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supporting information
p. 3546 - 3557
(2017/08/15)
-
- Biguanide probes and preparation method thereof
-
The invention provides compounds, a preparation method thereof, an application of the compounds in kit preparation, a method for screening drug targets and a method for determining whether the drug targets exist in a sample. Each compound contains an active group and a potential reporter group, wherein the active group has a structure represented as a formula in the description, and the potential reporter group is alkynyl. The compounds can specifically identify and be bound with in-vivo acting targets of biguanides without affecting cell permeability and facilitate observation, separation and purification of target protein. The compounds further have activity of biguanides, and have great significance on study of the in-vivo acting targets of biguanides as well as structural information such as action modes of drugs and the targets, active sites and the like.
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Paragraph 0057-0060
(2018/03/28)
-
- An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines
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We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.
- H?ring, Andreas P.,Biallas, Phillip,Kirsch, Stefan F.
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p. 1526 - 1539
(2017/04/01)
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- Chemoselective N-acetylation of primary aliphatic amines promoted by pivalic or acetic acid using ethyl acetate as an acetyl donor
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The combination of pivalic or acetic acid as a promoter and EtOAc as a solvent and acetyl donor proved to be efficient for the chemoselective N-acetylation of primary aliphatic amines to afford the corresponding acetamides. We developed a simple and convenient approach, which requires mild reaction conditions. Competitive inter- and intramolecular reactions between aliphatic amines, alcohols, and aromatic amines were examined, and chemoselectivity was achieved by adjusting the conditions of the reaction.
- Yoshida, Tomoki,Kawamura, Shimpei,Nakata, Kenya
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supporting information
p. 1181 - 1184
(2017/03/02)
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- An unexpected copper-catalyzed carbonylative acetylation of amines
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A novel copper-catalyzed carbonylative acetylation of amines has been developed. With peroxide as the oxidant as well as the methyl source with a copper catalyst under CO pressure, good yields of N-acetyl amides could be obtained. Notably, this is the first example of carbonylative acetylation.
- Li, Yahui,Wang, Changsheng,Zhu, Fengxiang,Wang, Zechao,Fran?ois Soulé, Jean,Dixneuf, Pierre H.,Wu, Xiao-Feng
-
supporting information
p. 142 - 144
(2016/12/27)
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- Application of Imine Reductases (IREDs) in Micro-Aqueous Reaction Systems
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Here we present the applicability of different imine reductases (IREDs) in micro-aqueous reaction systems. Subjects of the study were the IREDs from Streptomyces aurantiacus (SaIR), Streptomyces sp. GF3587 (RGF3587IR), Streptomyces kanamyceticus (SkIR), Streptomyces ipomoeae 91-03 (SiIR), Streptomyces sp. GF3546 (SGF3546IR), and Paenibacillus elgii B69 (PeIR). The IREDs were overexpressed in Escherichia coli (E. coli) cells and used directly after lyophilization. Several organic solvents and buffer amounts were screened for the reduction of the two substrates β-carboline harmane and 1-methyl-3,4-dihydroisoquinoline to the corresponding amines. Cyclopentyl methyl ether (CPME) proved to be the best solvent choice for the envisaged reduction. In addition, CPME is currently referred to as an environmentally benign solvent. Optimized reaction conditions were applied to 20 mM of the hardly water soluble substrates, leading to good conversions (up to 96%) and excellent enantiomeric excesses (>99%) in the best cases. The use of micro-aqueous reaction systems opens the way to further applications of IREDs with hardly water soluble substrates. (Figure presented.).
- Maugeri, Zaira,Rother, D?rte
-
supporting information
p. 2745 - 2750
(2016/09/13)
-
- Bis-arylalkenylalkyl acid compound, and preparation method and application thereof
-
The invention relates to a bis-arylalkenylalkyl acid compound, and a preparation method and an application thereof. The structure of the compound is represented by the formula I. the definitions of *, R1, R2, R3, n1 and m are as in the specifications and the claims. The bis-arylalkenylalkyl acid compound provided by the invention has relatively high inhibition activity against sensitive strains and resistant strains, and can be used for preparing antibacterial drugs.
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Paragraph 0114; 0115; 0116; 0117
(2016/10/07)
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- Product-Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides
-
A novel product-derived bimetallic palladium complex catalyzes a sulfonylazide-transfer reaction with the σ-donor/π-acceptor ligand CO, and is advantageous given its broad substrate scope, high efficiency, and mild reaction conditions (atmospheric pressure of CO at room temperature). This methodology provides a new approach to sulfonylureas, which are present in both pharmaceuticals and agrochemicals. The synthesis of Glibenclamide on a gram scale further revealed the practical utility of this procedure. Mechanistically, the generation of a bridged bimetallic palladium species derived from the product sulfonylurea is disclosed as the crucial step for this catalytic cycle.
- Zhao, Jin,Li, Zongyang,Song, Shaole,Wang, Ming-An,Fu, Bin,Zhang, Zhenhua
-
supporting information
p. 5545 - 5549
(2016/05/09)
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- Efficient and selective N-, S- and O-acetylation in TEAA ionic liquid as green solvent. Applications in synthetic carbohydrate chemistry
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Background: The ionic liquid triethylammonium acetate (TEAA) was found to be an efficient solvent in the acetylation of alcohols, amines, oximes and thiols to their corresponding acetyl compounds using only a 10% excess of acetic anhydride under mild conditions. Moreover TEAA is not only an inexpensive and recyclable solvent but also an anomeric selective catalyst in the per-O-acetylation of sugar moieties. Methods: Simple and effective organic synthesis protocols were provided for the selective acetylation of several substrates. The products were fully characterized by 1H and 13C NMR spectroscopy and the anomeric ratios were obtained from the 1H spectra. Results: Structurally diverse alcohols, phenols, thiols, amines, carbohydrates and oximes underwent acylation under mild conditions by this procedure to provide the corresponding acetates in excellent yields. TEAA ionic liquid is unique in its capability to act as both, solvent and high selective catalyst. As expected, the reaction proceeds with high b anomeric selectivity for sugars derivatives. Moreover, the ionic liquid was regenerated, recycled and reused for three times without apparent loss of reactivity and selectivity in all cases. Conclusions: The present procedure provides a powerful and versatile acylation method for alcohols, phenols, thiols, amines, oximes and carbohydrates. This protocol is endowed with several unique merits: selectivity, cost-efficiency, atom-economy and mild reaction conditions tolerable to acid sensitive functionalities. With these features, this method may be considered as a better alternative for the acetylation of a wide range of substrates.
- Lafuente, Leticia,Díaz, Gisela,Bravo, Rodolfo,Ponzinibbio, Agustín
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p. 195 - 200
(2016/02/26)
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- Competitive Deprotonation and Superoxide [O2 -?] Radical-Anion Adduct Formation Reactions of Carboxamides under Negative-Ion Atmospheric-Pressure Helium-Plasma Ionization (HePI) Conditions
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Carboxamides bearing an N-H functionality are known to undergo deprotonation under negative-ion-generating mass spectrometric conditions. Herein, we report that N-H bearing carboxamides with acidities lower than that of the hydroperoxyl radical (HO-O?) preferentially form superoxide radical-anion (O2 -?) adducts, rather than deprotonate, when they are exposed to the glow discharge of a helium-plasma ionization source. For example, the spectra of N-alkylacetamides show peaks for superoxide radical-anion (O2 -?) adducts. Conversely, more acidic amides, such as N-alkyltrifluoroacetamides, preferentially undergo deprotonation under similar experimental conditions. Upon collisional activation, the O2 -? adducts of N-alkylacetamides either lose the neutral amide or the hydroperoxyl radical (HO-O?) to generate the superoxide radical-anion (m/z 32) or the deprotonated amide [m/z (M - H)-], respectively. For somewhat acidic carboxamides, the association between the two entities is weak. Thus, upon mildest collisional activation, the adduct dissociates to eject the superoxide anion. Superoxide-adduct formation results are useful for structure determination purposes because carboxamides devoid of a N-H functionality undergo neither deprotonation nor adduct formation under HePI conditions. [Figure not available: see fulltext.]
- Hassan, Isra,Pinto, Spencer,Weisbecker, Carl,Attygalle, Athula B.
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p. 394 - 401
(2016/02/23)
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- Synthesis process of glibenclamide intermediate 4-Acetamidobenzenesulfonamide
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The invention aims at providing a synthesis process of glibenclamide intermediate 4-Acetamidobenzenesulfonamide. The synthesis process is characterized by comprising the following steps that 1, a crude acetyl phenethylamine acyl compound product is prepared, namely phenethylamine and acetic anhydride perform acylation reaction; 2, acetylamino-benzenesulfonyl chloride is prepared, namely an acetyl phenethylamine acyl compound and chlorosulfonic acid perform chlorosulfonation reaction; 3, the 4-Acetamidobenzenesulfonamide is prepared, namely the acetylamino-benzenesulfonyl chloride and ammonia water perform reaction; The synthesis process has the advantages that by changing the proportion of reactants and reaction conditions, the yield of the glibenclamide intermediate 4-Acetamidobenzenesulfonamide is improved, and further the glyburide yield is improved.
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Paragraph 0033; 0034
(2016/11/07)
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- Mild and efficient preparation method of alpha-acyloxy alkenyl amide compound and application thereof to synthesis of amide and polypeptide
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The invention discloses a mild and efficient preparation method of an alpha-acyloxy alkenyl amide compound and application thereof to synthesis of an amide and a polypeptide. The alpha-acyloxy alkenyl amide compound is obtained by an addition reaction of alkyne amide and carboxylic acid in dichloromethane under a condition that the temperature is 0 to 50 DEG C; the product alpha-acyloxy alkenyl amide compound can generate the amide or the polypeptide with amides through combination reaction; the two reactions can be carried out step by step and can also be carried out in one pot; when the two reactions are carried out in one pot, the product alpha-acyloxy alkenyl amide compound does not need to be purified from the former reaction and the amide compound is directly added to react, wherein in the reaction of generating the amide or the polypeptide, a solvent can also be water, so that a novel method for fixed-site decoration and marking of biological macromolecules including proteins, nucleic acid and the like in a water phase is provided. The mild and efficient preparation method has moderate reaction conditions and does not need a metal catalyst; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; the mild and efficient preparation method is simple to operate and wide in application range.
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Paragraph 0018; 0019
(2017/05/16)
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- Ynamides as Racemization-Free Coupling Reagents for Amide and Peptide Synthesis
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A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH2, ArNH2, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.
- Hu, Long,Xu, Silin,Zhao, Zhenguang,Yang, Yang,Peng, Zhiyuan,Yang, Ming,Wang, Changliu,Zhao, Junfeng
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supporting information
p. 13135 - 13138
(2016/10/22)
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- Phosphovanadomolybdic acid catalyzed desulfurization-oxygenation of secondary and tertiary thioamides into amides using molecular oxygen as the terminal oxidant
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In the presence of phosphovanadomolybdic acids, e.g., H6PV3Mo9O40, desulfurization-oxygenation of various kinds of structurally diverse secondary and tertiary thioamides proceeded efficiently using molecular oxygen as the terminal oxidant, affording the corresponding amides in moderate to excellent yields. In addition, 18O-labeled amides could readily be synthesized using H218O as the oxygen source.
- Xu, Ning,Jin, Xiongjie,Suzuki, Kosuke,Yamaguchi, Kazuya,Mizuno, Noritaka
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p. 4865 - 4869
(2016/07/06)
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- N-Acyl-N-(4-chlorophenyl)-4-nitrobenzenesulfonamides: Highly selective and efficient reagents for acylation of amines in water
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A variety of N-acyl-N-(4-chlorophenyl)-4-nitrobenzenesulfonamides (1a-e) were synthesized in one pot from 4-chloroaniline under solvent-free conditions and have been developed as chemoselective N-acylation reagents. Selective protection of primary amines in the presence of secondary amines, acylation of aliphatic amines in the presence of aryl amines, and monofunctionalization of primary-secondary diamines as well as selective N-acylation of amino alcohols using these reagents are described. All of the acylation reactions were carried out in water as a green solvent. High stability and easy preparation of these acylating reagents are other advantages of this method.
- Ebrahimi, Sara,Saiadi, Safoura,Dakhilpour, Simin,Mirsattari, Seyed Nezamoddin,Massah, Ahmad Reza
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- Potassium Thioacids Mediated Selective Amide and Peptide Constructions Enabled by Visible Light Photoredox Catalysis
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A remarkable visible-light-promoted photoredox catalytic methodology involved with amines and eco-friendly potassium thioacids for amide formation was uncovered. This approach can mimic the natural coenzyme acetyl-CoA to selectively acylate amines without affecting other functional groups such as alcohols, phenols, esters, among others. The developed strategy may hold great potential for a comprehensive display of biologically interesting peptide synthesis and amino acid modification through a diacyl disulfide intermediate.
- Liu, Hongxin,Zhao, Liyun,Yuan, Yunfei,Xu, Zhifang,Chen, Kai,Qiu, Shengxiang,Tan, Haibo
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p. 1732 - 1736
(2016/03/15)
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- Virtual screening for novel Atg5-Atg16 complex inhibitors for autophagy modulation
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Two hit compounds (14 and 62) were identified using virtual high throughput screening (vHTS) inhibiting the autophagy process in A2780 ovarian cancer cells. The expression levels of the LC3-II and p62 autophagy marker proteins were monitored using Western blotting. Preliminary structure activity relationship (SAR) study of close structural analogues revealed another active compound 38. The three active compounds were tested in the MCF-7 human breast cancer cells and severe reduction of autophagosomes formation was observed confirming the activity of the inhibitors. The docking scaffold used for the vHTS was a lipophilic cleft on the Atg5 protein, which is occupied by a phenylalanine residue in the Atg16 polypeptide. To the best of our knowledge this is the first report on inhibitors that specifically modulate autophagy by directly inhibiting autophagy specific proteins, which is significant due the role autophagy plays in a number of morbid diseases such as cancer. This journal is
- Robinson, Elizabeth,Leung, Euphemia,Matuszek, Anna M.,Krogsgaard-Larsen, Niels,Furkert, Daniel P.,Brimble, Margaret A.,Richardson, Alan,Reynisson, Jhannes
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supporting information
p. 239 - 246
(2015/02/02)
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- A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines
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A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone. (Figure Presented).
- Luu, Hieu-Trinh,Wiesler, Stefan,Frey, Georg,Streuff, Jan
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supporting information
p. 2478 - 2481
(2015/05/27)
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- SUBSTITUTED DIAMINOPYRIMIDYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are diaminopyrimidyl Compounds having the following structures: wherein X, L, R1, and R2 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidyl Compound, and methods for treating or preventing PKC-theta-mediated disorders, or a condition treatable or preventable by inhibition of a kinase, for example, PKC-theta.
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Paragraph 0371
(2015/07/02)
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- A convenient formation of aporphine core via benzyne chemistry: Conformational analysis and synthesis of (R)-aporphine
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Total synthesis of (R)-aporphine has been accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2] cycloaddition reaction followed by a hydrogen migration, leading to aporphine core in good yield, which was subjected to a 1D gradient NOE experiment, conformational analysis, and simple transformations, including a small scale resolution process, to afford enantiomerically enriched aporphine alkaloid.
- Perecim, Givago P.,Rodrigues, Alessandro,Raminelli, Cristiano
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supporting information
p. 6848 - 6851
(2015/11/27)
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- An attractive route to transamidation catalysis: Facile synthesis of new o-aryloxide-N-heterocyclic carbene ruthenium(II) complexes containing trans triphenylphosphine donors
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Well-defined robust ruthenium(II) complexes 3a-d bearing o-aryloxide-N-heterocyclic carbene ligands with different wingtip substituents (3a (R = Me), 3b (R = Ph), 3c (R = iPr) and 3d (R = Mes)) in the imidazole ring were synthesized in good yields by the reaction of imidazolium proligands with metal precursor [RuHCl(CO)(PPh3)3] by transmetallation from the corresponding silver carbene complexes. All the Ru(II)-NHC complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. The molecular structure of the complex 3a was identified by means of single-crystal X-ray diffraction analysis, which revealed that the complexes possess a distorted octahedral geometry. In order to explore the catalytic potential of the synthesized complexes, all the four [Ru-NHC] complexes [3a-d] were tested as catalysts for transamidation of carboxamides with amines. Notably, the complex 3a was found to be very efficient and versatile catalyst toward transamidation of a wide range of amides with amines.
- Nirmala, Muthukumaran,Prakash, Govindan,Viswanathamurthi, Periasamy,Malecki, Jan Grzegorz
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- H-β-zeolite catalyzed transamidation of carboxamides, phthalimide, formamides and thioamides with amines under neat conditions
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Efficient transamidation of unactivated carboxamides, phthalimides, formamides and thioamides with amines under solvent-free conditions using H-β-zeolite as a green and recyclable heterogeneous catalyst is described. Easy work up, high purity of the products, recyclability and environmentally-friendly nature of the catalyst are the attractive features of the present methodology. This is the first report for the transamidation of thioamides under heterogeneous conditions.
- Rao, Sadu Nageswara,Chandra Mohan, Darapaneni,Adimurthy, Subbarayappa
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p. 95313 - 95317
(2015/11/24)
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- Copper-catalyzed redox-neutral C-H amination with amidoximes
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CuI-catalyzed reactions of N-alkylamidoximes afforded dihydroimidazoles via sp3 C-H amination. On the other hand, the reactions of N-benzoylamidoximes resulted in sp2 C-H amination to form quinazolinones. The reaction mechanisms could be characterized as a redox-neutral radical pathway including a Cu(i)-Cu(ii) redox catalytic cycle. The Royal Society of Chemistry.
- Chen, Hui,Chiba, Shunsuke
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- Green synthesis of benzamides in solvent- and activation-free conditions
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Herein, we describe a clean and ecocompatible pathway for both N-benzoylation and N-acetylation of anilines, amines, diamines, and aminoalcohols using three enol esters with good yields. We have improved the use of vinyl benzoate for the direct introduction of a benzamido-moiety under solvent- and activation-free conditions. The recovered amides are easily isolated by crystallization. Copyright
- Alalla, Affef,Merabet-Khelassi, Mounia,Aribi-Zouioueche, Louisa,Riant, Olivier
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supporting information
p. 2364 - 2376
(2014/07/22)
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- Tandem synthesis of amides and secondary amines from esters with primary amines under solvent-free conditions
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An iridium(III)-catalyzed tandem synthesis of amides and amines from esters under solvent-free conditions is described. A commercially available iridium(III) complex, [Cp*IrCl2]2, with sodium acetate showed the best activity for the synthesis of amides and secondary amines. The amide was formed by ester-amide exchange which generates an alcohol in situ which is subsequently transformed to a secondary amine via hydrogen autotransfer. This synthetic protocol with high atom economy generates water as the sole by-product and can afford amides and amines from various esters in a one-pot reaction, expanding the synthetic versatility of ester transformations.
- Lee, Jeongbin,Muthaiah, Senthilkumar,Hong, Soon Hyeok
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supporting information
p. 2653 - 2660
(2014/09/17)
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- Mechanistic and structural analysis of Drosophila melanogaster arylalkylamine N-acetyltransferases
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(Chemical Equation Presented). Arylalkylamine N-acetyltransferase (AANAT) catalyzes the penultimate step in the biosynthesis of melatonin and other N-acetylarylalkylamides from the corresponding arylalkylamine and acetyl-CoA. The N-acetylation of arylalkylamines is a critical step in Drosophila melanogaster for the inactivation of the bioactive amines and the sclerotization of the cuticle. Two AANAT variants (AANATA and AANATB) have been identified in D. melanogaster , in which AANATA differs from AANATB by the truncation of 35 amino acids from the N-terminus. We have expressed and purified both D. melanogaster AANAT variants (AANATA and AANATB) in Escherichia coli and used the purified enzymes to demonstrate that this N-terminal truncation does not affect the activity of the enzyme. Subsequent characterization of the kinetic and chemical mechanism of AANATA identified an ordered sequential mechanism, with acetyl-CoA binding first, followed by tyramine. We used a combination of pH-activity profiling and site-directed mutagenesis to study prospective residues believed to function in AANATA catalysis. These data led to an assignment of Glu-47 as the general base in catalysis with an apparent pKa of 7.0. Using the data generated for the kinetic mechanism, structure-function relationships, pH-rate profiles, and site-directed mutagenesis, we propose a chemical mechanism for AANATA.
- Dempsey, Daniel R.,Jeffries, Kristen A.,Bond, Jason D.,Carpenter, Anne-Marie,Rodriguez-Ospina, Santiago,Breydo, Leonid,Caswell, K. Kenneth,Merkler, David J.
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p. 7777 - 7793
(2015/02/19)
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