- Design, synthesis, biological evaluation and molecular modeling studies of novel eugenol esters as leishmanicidal agents
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Leishmaniasis is a neglected pathology with a high incidence worldwide, and is a governmental health issue due to the increased morbidity and mortality associated with the disease and a scarce therapeutic arsenal. Cysteine proteases have been investigated
- Coelho, Camila M.,Dos Santos, Thiago,Freitas, Poliany G.,Nunes, Juliana B.,Marques, Marcos J.,Padovani, Camila G. D.,Júdice, Wagner A. S.,Camps, Ihosvany,Da Silveira, Nelson J. F.,Carvalho, Diogo T.,Veloso, Marcia P.
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- Essential oil-based design and development of novel anti-Candida azoles formulation
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Candida is the most common fungal class, causing both superficial and invasive diseases in humans. Although Candida albicans is the most common cause of fungal infections in humans, C. auris is a new emergent serious pathogen causing complications similar to those of C. albicans. Both C. albicans and C. auris are associated with high mortality rates, mainly because of their multidrug-resistance patterns against most available antifungal drugs. Although several compounds were designed against C. albicans, very few or none were tested on C. auris. Therefore, it is urgent to develop novel effective antifungal drugs that can accommodate not only C. albicans, but also other Candida spp., particularly newly emergent one, including C. auris. Inspired by the significant broad-spectrum antifungal activities of the essential oil cuminaldehyde and the reported wide incorporation of azoles in the antifungal drugs, a series of compounds (UoST1-11) was designed and developed. The new compounds were designed to overcome the toxicity of the aldehyde group of cuminaldehyde and benefit from the antifungal selectivity of azoles. The new developed UoST compounds showed significant anti-Candida activities against both Candida species. The best candidate compound, UoST5, was further formulated into polymeric nanoparticles (NPs). The new formula, UoST5-NPs, showed similar activities to the nanoparticles-free drug, while providing only 25% release after 24 h, maintainng prolonged activity up to 48 h and affording no toxicity. In conclusion, new azole formulations with significantly enhanced activities against C. albicans and C. auris, while maintaining prolonged action and no toxicities at lower concentrations, were developed.
- Fayed, Bahgat,Haider, Mohamed,Hamdy, Rania,Hamoda, Alshaimaa M.,Rawas-Qalaji, Mutasem,Soliman, Sameh S. M.
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- Facile synthesis of polyamide dendrimers from unprotected AB2 building blocks: Dumbbell-shaped dendrimer, star-shaped dendrimer, and dendrimer with a carboxylic acid at the core
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A fast, inexpensive, and highly efficient synthesis of aromatic polyamide dendrimers, without the need for protection and deprotection steps, has been developed. Dendrons and various types of polyamide dendrimers were easily prepared by a convergent appro
- Washio, Isao,Shibasaki, Yuji,Ueda, Mitsuru
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- Synthesis, photophysical, electrochemical and electroluminescent properties of a novel iridium(III) complex based on 2-phenylbenzo[d]oxazole derivative
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A new phosphorescent iridium (III) complex based on 2-(4-tert-butylphenyl)- 5-methylbenzo[d]oxazole as main ligand, i.e. bis(2-(4-tert-butylphenyl)-5- methylbenzo[ d]oxazole-N,C2′)iridium(acetylacetonate) [(tmbo)2Ir(acac)], was synth
- Li, Xiao,Yu, Xiao-Ting,Chi, Hai-Jun,Dong, Yan,Xiao, Guo-Yong,Lei, Peng,Zhang, Dong-Yu,Cui, Zheng
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- Synthesis and Characterization of Copper Complexes with the N-(2,6-Diisopropylphenyl)-N′-acylthiourea Ligands
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Three N-(2,6-diisopropylphenyl)-N′-acylthiourea ligands [Ar′NHC(S)NHC(O)Ar; Ar′ = 2,6-iPr2C6H3; Ar = p-tBuC6H4 (1, L1), Mes (2, L2), and 1-Naph (3, L3)] were synthesized and compared with the homologous ligand L0 (Ar = Ph) in terms of their resultant complexes with copper halides. The reaction of L1 with CuCl2 led to the formation of mononuclear L12CuCl (4), while treatment of L1 with CuX (X = Cl, Br) resulted in the adamantane cage complexes (L1CuX)4 (X = Cl, 5; Br, 6). These findings are similar to the results shown by its parent ligand L0. The reaction of L1 with CuI yielded the iodide-bridged dimeric complex [L12Cu(μ-I)]2 (7), in contrast to the ligand-bridged dimer supported by L0. L2 readily afforded the mononuclear CuI complexes 8–10 coordinated by two or three ligands. L3 gave monomeric L33CuX (X = Cl, 11; Br, 12) and the iodide-bridged dimeric [L32Cu(μ-I)]2 (13). L3 can bind with CuI halides in a ratio of 1:1 to give complexes L3CuX(PPh3)2 (14–16), when Cu2X2(PPh3)3 (X = Cl, Br) or CuI(PPh3)3 were used as precursors. Treatment of (L1CuCl)4 (5), L22CuBr (8), and L33CuCl (11), respectively, with hot EtOH resulted in the formation of trans-CuLn′2 (17–19) compounds. All compounds were characterized by single-crystal X-ray diffraction studies.
- Wang, Dan,Wu, Su-Yun,Li, Hai-Pu,Yang, Ying,Roesky, Herbert W.
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- A targeted delivery strategy for the development of potent trypanocides
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A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against Trypanosoma brucei, the causative agent of African sleeping sickness. Thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite.
- Gordhan, Heeren M.,Milanes, Jillian E.,Qiu, Yijian,Golden, Jennifer E.,Christensen, Kenneth A.,Morris, James C.,Whitehead, Daniel C.
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- One-step Conversion of Amides and Esters to Acid Chlorides with PCl3
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A general and efficient iodine-promoted chlorination of amides and esters with phosphorus trichloride is described. For the first time. Various inactivated amides including secondary and tertiary amides were directly converted to the corresponding acid chlorides in one-step. The substrate scope of methyl esters including aromatic and aliphatic esters was also explored under this system. This method is simple, scalable and wide in scope, which provides an approach to preparation of these acid chlorides.
- Li, Fangshao,Wu, Xiaofang,Guo, Fengzhe,Tang, Zi-Long,Xiao, Jing
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supporting information
p. 4314 - 4317
(2021/07/16)
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- Synthesis and molecular docking studies of some novel antimicrobial benzamides
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Common use of classical antibiotics has caused to the growing emergence of many resistant strains of pathogenic bacteria. Therefore, we aimed to synthesize a number of N-(2-hydroxy-(4 or 5)-nitrophenyl)benzamide derivatives as a new class of antimicrobial compounds. Moreover, our second goal is to predict the interaction between active structures and enzymes (DNA –gyrase and FtsA) in the binding mode. In this study, thirteen N-(2-hydroxy-(4 or 5-nitrophenyl)-substituted-benzamides were synthesized and determined for their antimicrobial activity using the microdilution method. According to this work, none of the compounds showed any activity against Candida albicans and its clinical isolate. Some of the benzamides (4N1, 5N1, 5N2) displayed very significant activity against Staphylococcus aureus and MSSA with 4 μg/ml MIC value, even they were found to be more potent than ceftazidime. 4N1 was also found to be more effective than gentamicin against Enterococcus faecalis clinical isolate. Molecular docking studies revealed that 4N1, 5N1, and 5N2 showed a good interactions with DNA-gyrase. Moreover, 5N1 has interacted with FtsA enzyme in the binding mode, as well. Only compound 5N4 displayed very good activity against Escherichia coli ATCC 25922. These findings showed us that 4N1, 5N1, 5N2, and 5N4 could be lead compounds to discover new antibacterial candidates against multidrug-resistant strains.
- Acar, Cemre,Yal??n, Gozde,Ertan-Bolelli, Tu?ba,Kaynak Onurda?, Fatma,?kten, Suzan,?ener, Funda,Y?ld?z, ?lkay
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- Electrochemical intramolecular C-H/N-H functionalization for the synthesis of isoxazolidine-fused isoquinolin-1(2: H)-ones
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A general and practical protocol for the construction of isoxazolidine-fused isoquinolin-1(2H)-ones has been described by electrochemical-oxidation-induced intramolecular annulation via amidyl radicals. In an undivided cell, isoquinolinones could be easily generated from various available amides bearing CONHOR groups under metal-free, additive-free and external oxidant-free conditions. Moreover, this transformation proceeded smoothly by using cheap 95% ethanol as the green solvent and could be extended to the gram scale.
- Zhang, Lin-Bao,Geng, Rui-Sen,Wang, Zi-Chen,Ren, Guang-Yi,Wen, Li-Rong,Li, Ming
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supporting information
p. 16 - 21
(2020/01/13)
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- Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
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An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
- Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
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supporting information
p. 17887 - 17896
(2020/08/19)
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- 3-(2,6-difluorophenyl)-1,2,4-oxadiazole compound and application thereof
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The invention provides a 3-(2,6-difluorophenyl)-1,2,4-oxadiazole compound insecticide/acaricide with a structure as shown in a general formula I in the specification, wherein R is as shown in the specification. The compound as shown in the general formula
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Paragraph 0028; 0032-0034
(2019/02/25)
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- Electrooxidative amination of sp2 C-H bonds: Coupling of amines with aryl amides via copper catalysis
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Metal-catalyzed cross-coupling reactions are among the most important transformations in organic synthesis. However, the use of C-H activation for sp2 C-N bond formation remains one of the major challenges in the field of cross-coupling chemistry. Described herein is the first example of the synergistic combination of copper catalysis and electrocatalysis for aryl C-H amination under mild reaction conditions in an atom-and step-economical manner with the liberation of H2 as the sole and benign byproduct.
- Kathiravan, Subban,Suriyanarayanan, Subramanian,Nicholls, Ian A.
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supporting information
p. 1968 - 1972
(2019/03/07)
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- Identification of Anti-Mycobacterial Biofilm Agents Based on the 2-Aminoimidazole Scaffold
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Tuberculosis (TB) remains a significant global health problem for which new therapeutic options are sorely needed. The ability of the causative agent, Mycobacterium tuberculosis, to reside within host macrophages and form biofilm-like communities contributes to the persistent and drug-tolerant nature of the disease. Compounds that can prevent or reverse the biofilm-like phenotype have the potential to serve alongside TB antibiotics to overcome this tolerance, and decrease treatment duration. Using Mycobacterium smegmatis as a surrogate organism, we report the identification of two new 2-aminoimidazole compounds that inhibit and disperse mycobacterial biofilms, work synergistically with isoniazid and rifampicin to eradicate preformed M. smegmatis biofilms in vitro, are nontoxic toward Galleria mellonella, and exhibit stability in mouse plasma.
- Nguyen, T. Vu,Minrovic, Bradley M.,Melander, Roberta J.,Melander, Christian
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p. 927 - 937
(2019/03/26)
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- Palladium-Catalyzed Electrochemical C-H Bromination Using NH4Br as the Brominating Reagent
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The palladium-catalyzed electrochemical C-H bromination of benzamide derivatives under divided cells is developed, in which NH4Br serves as a brominating reagent and electrolyte. The protocol avoids the use of chemical oxidants and provides an alternative method for the synthesis of aryl bromides.
- Yang, Qi-Liang,Wang, Xiang-Yang,Wang, Tong-Lin,Yang, Xiang,Liu, Dong,Tong, Xiaofeng,Wu, Xin-Yan,Mei, Tian-Sheng
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supporting information
p. 2645 - 2649
(2019/04/17)
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- Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold
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Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158?mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059?mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.
- Zhu, Xiang,Zhang, Min,Yu, Linhua,Xu, Zhihong,Yang, Dan,Du, Xiaoying,Wu, Qinglai,Li, Junkai
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supporting information
p. 2453 - 2460
(2018/03/29)
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- Ligand-Promoted RhIII-Catalyzed Thiolation of Benzamides with a Broad Disulfide Scope
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A ligand-promoted RhIII-catalyzed C(sp2)?H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII-catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.
- Kang, Yan-Shang,Zhang, Ping,Li, Min-Yan,Chen, You-Ke,Xu, Hua-Jin,Zhao, Jing,Sun, Wei-Yin,Yu, Jin-Quan,Lu, Yi
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supporting information
p. 9099 - 9103
(2019/06/13)
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- Cu-Mediated C-H Thioetherification of Arenes at Room Temperature
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Cu-mediated C-H thioetherification of arenes with ethylene sulfide has been developed using a readily removable directing group. The reaction proceeded at room temperature, and a variety of sensitive functional groups including chloro, bromo, and vinyl were well tolerated. The thiolated products could be converted to the seven-membered benzoxathiepinones derivatives by a sequence of hydrolysis-lactonization reactions.
- Wang, Xing,Yi, Xing,Xu, Hui,Dai, Hui-Xiong
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supporting information
p. 5981 - 5985
(2019/08/26)
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- Hydrogen Bond Directed ortho-Selective C?H Borylation of Secondary Aromatic Amides
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Reported is an iridium catalyst for ortho-selective C?H borylation of challenging secondary aromatic amide substrates, and the regioselectivity is controlled by hydrogen-bond interactions. The BAIPy-Ir catalyst forms three hydrogen bonds with the substrate during the crucial activation step, and allows ortho-C?H borylation with high selectivity. The catalyst displays unprecedented ortho selectivities for a wide variety of substrates that differ in electronic and steric properties, and the catalyst tolerates various functional groups. The regioselective C?H borylation catalyst is readily accessible and converts substrates on gram scale with high selectivity and conversion.
- Bai, Shao-Tao,Bheeter, Charles B.,Reek, Joost N. H.
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supporting information
p. 13039 - 13043
(2019/07/31)
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- Asymmetric Palladium-Catalyzed C-H Functionalization Cascade for Synthesis of Chiral 3,4-Dihydroisoquinolones
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A palladium-catalyzed C-H functionalization/intramolecular asymmetric allylation cascade of N-sulfonyl benzamides with 1,3-dienes has been developed. In the presence of a chiral pyridine-oxazoline ligand, this protocol enables the synthesis of chiral 3,4-dihydroisoquinolones in yields of up to 83% with enantioselectivities of up to 96%, using environmentally friendly air as the terminal oxidant.
- Sun, Manman,Wu, Haijian,Xia, Xiangyu,Chen, Weida,Wang, Zhiming,Yang, Jianguo
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p. 12835 - 12847
(2019/11/02)
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- 1, 8-naphthalimide amide compound and application thereof
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The invention discloses a 1, 8-naphthalimide amide compound and a synthesizing and application method thereof. The structural formula of the 1, 8-naphthalimide amide compound is shown as the formula I, wherein R is selected from A, B, C or D. The 1, 8-nap
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Paragraph 0022; 0026-0028
(2018/08/28)
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- NOVEL IRREVERSIBLE BRUTON'S TYROSINE KINASE INHIBITOR
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The present invention provides an inhibitor of Bruton's tyrosine kinase, which is a compound of formula (I), or its pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug. The present invention also provides a pharmaceutical composition comprsing the compound. The present invention also provides a method for inhibiting the activity of tyrosine kinase activity or for treating a disease, disorder, or condition, which would benefit from the inhibition of Bruton's tyrosine kinase(s), by using the Bruton's tyrosine kinase inhibitor, as well as application of the Bruton's tyrosine kinase inhibitor for the same.
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Paragraph 0104; 0107
(2019/01/04)
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- An Efficient Synthesis of New 2-Aryl-5-phenylazenyl-1,3,4-oxadiazole Derivatives from N, N' -Diarylcarbonohydrazides
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A series of new 1,3,4-oxadiazoles conjugated to aromatic substituents by an azo linker was synthesized in a four-step reaction sequence, involving cyclodehydration of a N, N' -diacylhydrazine fragment and dehydrogenation of the neighboring hydrazine fragm
- Kedzia, Anna,Jasiak, Karolina,Kudelko, Agnieszka
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supporting information
p. 1745 - 1748
(2018/06/26)
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- CoIII-Catalyzed Isonitrile Insertion/Acyl Group Migration Between C?H and N?H bonds of Arylamides
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A general efficient and site-selective cobalt-catalyzed insertion of isonitrile into C?H and N?H bonds of arylamides through C?H bond activation and alcohol assisted intramolecular trans-amidation is demonstrated. This straightforward approach overcomes the limitation by the presence of strongly chelating groups. Isolation of CoIII-isonitrile complex B has been achieved for the first time to understand the reaction mechanism.
- Kalsi, Deepti,Barsu, Nagaraju,Sundararaju, Basker
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supporting information
p. 2360 - 2364
(2018/02/22)
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- Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites
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The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation 100 μM and 50% parasite growth 2 μM. Four compounds showed nanomolar parasite growth inhibition activities, no cross-resistance in a chloroquine resistant strain and low cytotoxicity. QSAR analysis showed a strong association of parasite growth inhibition with inhibition of β-hematin formation and the most active compound inhibited hemozoin formation in P. falciparum, with consequent increasing exchangeable heme. Pioneering use of molecular docking for this system demonstrated predictive ability and could rationalize observed structure activity trends.
- L'abbate, Fabrizio P.,Müller, Ronel,Openshaw, Roxanne,Combrinck, Jill M.,de Villiers, Katherine A.,Hunter, Roger,Egan, Timothy J.
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p. 243 - 254
(2018/10/15)
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- Synthesis of phthalic acid derivatives: Via Pd-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates
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A Pd(ii)-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates has been developed. A broad range of benzamides and alkyl chloroformates are compatible with this protocol. The reaction is operationally simple and scalable. The direct group could be readily removed to access substituted phthalic acid esters (PAEs), 1,2-dibenzyl alcohols and phthalamides. Besides alkoxycarbonylation of benzamide β-C-H bonds, γ-alkoxycarbonylation of 2-phenylacetamide is also feasible.
- Liao, Gang,Chen, Hao-Ming,Shi, Bing-Feng
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supporting information
p. 10859 - 10862
(2018/10/02)
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- Visible-Light-Mediated Iminyl Radical Generation from Benzyl Oxime Ether: Synthesis of Pyrroline via Hydroimination Cyclization
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The treatment of an O-(4-methoxybenzyl) oxime ether bearing an olefin substituent and 1-chloroanthraquinone (1-Cl-AQN) catalyst in 2-butanone under visible-light irradiation affords pyrroline via an iminyl radical intramolecular hydroimination. Mechanistic studies indicate that iminyl radical generation mainly proceeds by hydrogen abstraction of the photocatalyst from the benzyl position of the oxime. Moreover, the hydrogen atom was identified in circulation from the benzylic position of the substrates between AQN and 2-butanone to quench the carbon radical without requiring any additional reagents.
- Usami, Kaoru,Yamaguchi, Eiji,Tada, Norihiro,Itoh, Akichika
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supporting information
p. 5714 - 5717
(2018/09/21)
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- Copper-Mediated Cyanation of Aryl C—H Bond with Removable Bidenate Auxiliary Using Acetonitrile as the Cyano Source
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Copper-mediated cyanation of aryl C—H bond with removable bidenate auxiliary as a directing group has been developed, in which green and cheap acetonitrile is used as the “CN” source. By switching the reaction conditions, the C—H cyanated products and N-Ar-phthalimides can be provided in acceptable yields with high chemoselectivity, respectively. The use of quaternary ammonium salt is essential for cyanation reaction.
- Yu, Zhengwei,Zhang, Saisai,Shen, Zengming
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supporting information
p. 1139 - 1142
(2018/10/15)
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- Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature
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Methods for the direct synthesis of difluoromethylated arenes are sparse, despite the importance of the difluoromethyl group in medical, agro-, and materials chemistry. A palladium-catalyzed decarbonylative cross-coupling reaction of acid chlorides with a difluoromethyl zinc reagent is achieved to access difluoromethylated compounds. The transformation proceeds at room temperature and shows broad functional group tolerance, thus providing a general and efficient method for decarbonylative difluoromethylation of a wide range of aromatic carboxylic acids.
- Pan, Fei,Boursalian, Gregory B.,Ritter, Tobias
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supporting information
p. 16871 - 16876
(2018/11/23)
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- Lanthanoid complexes supported by retro-Claisen condensation products of β-triketonates
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β-Triketonates have been recently used as chelating ligands for lanthanoid ions, presenting unique structures varying from polynuclear assemblies to polymers. In an effort to overcome low solubility of the complexes of tribenzoylmethane, four β-triketones with higher lipophilicity were synthesised. Complexation reactions were performed for each of these molecules using different alkaline bases in alcoholic media. X-ray diffraction studies suggested that the ligands were undergoing decomposition under the reaction conditions. This is proposed to be caused by in situ retro-Claisen condensation reactions, consistent with two examples that have been reported previously. The lability of the lanthanoid cations in the presence of a varying set of potential ligands gave rise to structures where one, two, or three of the molecules involved in the retro-Claisen condensation reaction were linked to the lanthanoid centres. These results, along with measurements of ligand decomposition in the presence of base alone, suggest the solvent used will modulate the impact of the retro-Claisen condensation in these complexes.
- Abad Galán, Laura,Sobolev, Alexandre N.,Zysman-Colman, Eli,Ogden, Mark I.,Massi, Massimiliano
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p. 17469 - 17478
(2019/01/03)
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- A General Cp*CoIII-Catalyzed Intramolecular C?H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids
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Herein, we report a Cp*CoIII-catalyzed C?H activation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine, and tylophora alkaloids. This particular C?H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion.
- Lerchen, Andreas,Knecht, Tobias,Koy, Maximilian,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 12149 - 12152
(2017/09/13)
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- Anhydrides from aldehydes or alcohols via oxidative cross-coupling
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A novel type of metal-free oxidative cross-coupling for the synthesis of symmetrical and mixed anhydrides from aldehydes or benzylic alcohols has been developed. The aldehydes or alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with an array of carboxylic acids. The methodology has a general applicability, and was successfully employed to prepare either aromatic or aliphatic symmetrical anhydrides and mixed anhydrides, which are very unstable compounds.
- Gaspa, Silvia,Amura, Ida,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 931 - 939
(2017/02/10)
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- Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides
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A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 2533 - 2536
(2017/06/13)
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- C-F bond cleavage enabled redox-neutral [4+1] annulation via C-H bond activation
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Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
- Wang, Cheng-Qiang,Ye, Lu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 1762 - 1765
(2017/02/15)
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- Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor
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Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7?nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35)?=?0.00) among 468 kinases/mutants at the concentration of 1?μM. Compound 9 completely abolished BMX, JAK3 and EGFR's activity. Both X-ray crystal structure and cysteine-serine mutation mediated rescue experiment confirmed 9's irreversible binding mode. 9 also potently inhibited BTK Y223 auto-phosphorylation (EC50: 30?nM), arrested cell cycle in G0/G1 phase and induced apoptosis in U2932 and Pfeiffer cells. We believe these features would make 9 a good pharmacological tool to study the BTK related pathology.
- Liang, Qianmao,Chen, Yongfei,Yu, Kailin,Chen, Cheng,Zhang, Shouxiang,Wang, Aoli,Wang, Wei,Wu, Hong,Liu, Xiaochuan,Wang, Beilei,Wang, Li,Hu, Zhenquan,Wang, Wenchao,Ren, Tao,Zhang, Shanchun,Liu, Qingsong,Yun, Cai-Hong,Liu, Jing
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p. 107 - 125
(2017/03/21)
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- Copper-Promoted Thiolation of C(sp2)–H Bonds Using a 2-Amino Alkylbenzimidazole Directing Group
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A copper-promoted thiolation of C(sp2)–H bonds with disulfides was achieved by using 2-amino alkylbenzimidazole (MBIP amine) as a new and removable N,N-bidentate directing group. This strategy gives a variety of functionalized thioethers in moderate to excellent yields in a simple and efficient way. Importantly, the substrate scope is not limited to aromatic amides; diverse alkenyl amides are also compatible. Furthermore, this synthetic approach provides a potentially feasible way to achieve structural modification of related benzimidazole-containing compounds through direct C–H activation.
- Liu, Shuang-Liang,Li, Xue-Hong,Shi, Tan-Hao,Yang, Guang-Chao,Wang, Hai-Li,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2280 - 2289
(2017/05/01)
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- General C-H Arylation Strategy for the Synthesis of Tunable Visible Light-Emitting Benzo[a]imidazo[2,1,5-c,d]indolizine Fluorophores
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Herein we report the discovery of the benzo[a]imidazo[2,1,5-c,d]indolizine motif displaying tunable emission covering most of the visible spectrum. The polycyclic core is obtained from readily available amides via a chemoselective process involving Tf2O-mediated amide cyclodehydration, followed by intramolecular C-H arylation. Additionally, these fluorescent heterocycles are easily functionalized using electrophilic reagents, enabling divergent access to varied substitution. The effects of said substitution on the compounds' photophysical properties were rationalized by density functional theory calculations. For some compounds, emission wavelengths are directly correlated to the substituent's Hammett constants. Easily introduced nonconjugated reactive functional groups allow the labeling of biomolecules without modification of emissive properties. This work provides a straightforward platform for the synthesis of new moderately bright fluorescent dyes remarkable for their chemical stability, predictability, and unusually high excitation-emission differential.
- Lévesque, éric,Bechara, William S.,Constantineau-Forget, Léa,Pelletier, Guillaume,Rachel, Natalie M.,Pelletier, Joelle N.,Charette, André B.
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p. 5046 - 5067
(2017/05/24)
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- Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides
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A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.
- Srimontree, Watchara,Chatupheeraphat, Adisak,Liao, Hsuan-Hung,Rueping, Magnus
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supporting information
p. 3091 - 3094
(2017/06/23)
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- Palladium-Nanoparticles-Catalyzed Oxidative Annulation of Benzamides with Alkynes for the Synthesis of Isoquinolones
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A novel method to synthesize isoquinolones via oxidative annulation of N-alkoxy benzamides and alkynes using binaphthyl-stabilized palladium nanoparticles (Pd-BNP) as catalyst has been developed. This methodology affords various isoquinolone derivatives in good to excellent yields with high regioselectivities in the presence of air as oxidant. N-Methoxybenzothioamide was also found to undergo oxidative annulation with alkyne successfully and provided a sulfur analogue of isoquinolones in moderate yields. The Pd-BNP catalyst was easily recovered and reused up to four times without any apparent agglomeration. (Figure presented.).
- Sharma, Nidhi,Saha, Rajib,Parveen, Naziya,Sekar, Govindasamy
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supporting information
p. 1947 - 1958
(2017/06/09)
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- Iron-catalyzed C-H/N-H activation by triazole guidance: Versatile alkyne annulation
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Iron-catalyzed C-H/N-H functionalizations were achieved by the aid of modular triazole amides. The alkyne annulation allowed for the expedient synthesis of valuable isoquinolone scaffolds with high levels of chemo-, site- and regio-selectivities.
- Cera,Haven,Ackermann
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supporting information
p. 6460 - 6463
(2017/07/10)
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- Nickel-Catalyzed Sulfonylation of C(sp2)–H Bonds with Sodium Sulfinates
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The first nickel-catalyzed ortho-sulfonylation of C(sp2)–H bonds with sodium sulfinates directed by (pyridin-2-yl)isopropylamine (PIP-amine) is described. This strategy exhibits a broad substrate scope and good functional group tolerance with high monosulfonylation selectivity. Besides arenes and heteroarenes, the reaction can also be extended to alkenes, providing diverse diaryl and alkyl aryl sulfones in high yields. Furthermore, a plausible Ni(I)/Ni(III) mechanism is outlined based on our experimental results and related precedents. (Figure presented.).
- Liu, Shuang-Liang,Li, Xue-Hong,Zhang, Shu-Sheng,Hou, Sheng-Kai,Yang, Guang-Chao,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2241 - 2246
(2017/07/07)
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- Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
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Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
- Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
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supporting information
p. 824 - 829
(2017/08/16)
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- C-H and N-H Bond Annulation of Benzamides with Isonitriles Catalyzed by Cobalt(III)
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A simple efficient, atom-economical procedure was developed for the cobalt-catalyzed C-H bond annulation of benzamides with isonitriles under mild conditions. The reaction tolerates a variety of functional group including heterocycles. Diverse 3-(alkylimino)-2-quinolin-8-yl-2,3-dihydro-1 H -isoindol-1-ones were synthesized using isonitriles as the C1 source through C-H and N-H bond annulation via C-H bond activation in a 'green' solvent. Vinylamides were also used similarly with tert -butyl isonitrile to give 3-(tert -butylimino)-1-quinolin-8-yl-1 H -pyrrol-2(5 H)-ones.
- Kalsi, Deepti,Barsu, Nagaraju,Dahiya, Pardeep,Sundararaju, Basker
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supporting information
p. 3937 - 3944
(2017/08/29)
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- MnCl2-Catalyzed C?H Alkylations with Alkyl Halides
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C?H alkylations with challenging β-hydrogen-containing alkyl halides were accomplished with sustainable MnCl2 as the catalyst under phosphine-ligand-free conditions. The proximity-induced benzamide C?H activation occurred with ample substrate s
- Liu, Weiping,Cera, Gianpiero,Oliveira, Jo?o C. A.,Shen, Zhigao,Ackermann, Lutz
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supporting information
p. 11524 - 11528
(2017/08/30)
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- Merging gold catalysis, organocatalytic oxidation, and Lewis acid catalysis for chemodivergent synthesis of functionalized oxazoles from: N -propargylamides
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Novel catalytic systems consisting of cationic gold complexes, N-hydroxyphthalimide (NHPI), and transition-metal-based Lewis acids have been developed for the one-pot synthesis of functionalized oxazoles from N-propargylamides with excellent functional group tolerance. These transformations demonstrated the excellent compatibility of homogeneous gold catalysis with organocatalytic oxidative carbon-nitrogen bond formations using tert-butyl nitrite as the terminal oxidant. Moreover, oxazolecarbonitriles or carboxamides can be easily synthesized in a one-pot protocol according to the different synthetic requirements.
- Mai, Shaoyu,Rao, Changqing,Chen, Ming,Su, Jihu,Du, Jiangfeng,Song, Qiuling
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supporting information
p. 10366 - 10369
(2017/09/25)
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- Ruthenium-Catalyzed Difluoroalkylation of 8-Aminoquinoline Amides at the C5-Position
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A ruthenium-catalyzed highly selective difluoromethylation of 8-aminoquinoline amides at the C5 position has been developed. It tolerates a broad range of functional groups, providing the corresponding difluoromethylated products in moderate to good yields. Preliminary experimental results indicate that the tricoordinate ruthenium intermediate is the key factor in achieving the C5-position selectivity.
- Chen, Changpeng,Zeng, Runsheng,Zhang, Jingyu,Zhao, Yingsheng
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supporting information
p. 6947 - 6950
(2017/12/26)
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- Synthesis and Antifungal Activity of Cuminic Acid Derivatives
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A series of benzamide derivatives (compounds 1–29) was synthesized based on the lead compound cuminic acid. The crystal structure of compound 11 was characterized by single crystal X-ray diffraction. The antifungal activity of the synthesized compounds wa
- Yang, Jian,Gao, Yang,Liu, Hui,Tang, Xiaorong
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p. 1112 - 1116
(2017/11/27)
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- Nickel-Catalyzed Decarbonylative Silylation, Borylation, and Amination of Arylamides via a Deamidative Reaction Pathway
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A nickel-catalyzed decarbonylative silylation, borylation, and amination of amides has been developed. This new methodology allows the direct interconversion of amides to arylsilanes, arylboronates, and arylamines and enables a facile route for carbon-heteroatom bond formations in a straightforward and mild fashion.
- Lee, Shao-Chi,Guo, Lin,Yue, Huifeng,Liao, Hsuan-Hung,Rueping, Magnus
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supporting information
p. 2594 - 2598
(2017/10/31)
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- Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides
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A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp2)-H functionalization of benzyl nitriles in the presence of activated C(sp3)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
- Das, Riki,Kapur, Manmohan
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p. 1114 - 1126
(2018/06/18)
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- ORGANIC METAL COMPOUND AND ORGANIC LIGHT-EMITTING DEVICE EMPLOYING THE SAME
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Organic metal compounds and organic electroluminescence devices employing the same are provided. The organic metal compound has a chemical structure represented below: wherein R1, R2, R3, R4, and R5 are independent and can be hydrogen, halogen, C1-8 alkyl or C1-8alkoxy; L can be acetylacetone ligand, picolinic acid ligand, N,N′-diisopropylbenzamidinate, or N,N′-diisopropyl-diisopropyl-guanidinate.
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- Metal-Free Oxidative Cross Esterification of Alcohols via Acyl Chloride Formation
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A novel metal-free oxidative cross esterification of alcohols has been achieved using trichloroisocyanuric acid as an oxidant. The alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with primary and secondary aliphatic, benzylic and allylic alcohols and phenols. A wide variety of esters was obtained in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 154 - 158
(2016/01/25)
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- Visible-Light-Mediated Synthesis of Amides from Aldehydes and Amines via in Situ Acid Chloride Formation
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An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate.
- Iqbal, Naeem,Cho, Eun Jin
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p. 1905 - 1911
(2016/03/15)
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- Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt-Catalyzed C-H Activation and Intramolecular Nucleophilic Addition
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A highly diastereoselective method for the synthesis of dihydroepoxybenzofluorenone derivatives from aromatic/vinylic amides and bicyclic alkenes is described. This new transformation proceeds through cobalt-catalyzed C-H activation and intramolecular nucleophilic addition to the amide functional group. Transition-metal-catalyzed C-H activation reactions of secondary amides with alkenes usually lead to [4+2] or [4+1] annulation; to the best of our knowledge, this is the first time that a [3+2] cycloaddition is described in this context. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. Mechanistic studies imply that the C-H bond cleavage may be the rate-limiting step. [3+2] instead of [4+2] or [4+1]: The diastereoselective [3+2] annulation of secondary amides with alkenes proceeds by cobalt-catalyzed C-H activation and intramolecular nucleophilic addition to the amide functional group under mild conditions. Mechanistic studies suggest that the C-H bond cleavage is the rate-limiting step.
- Gandeepan, Parthasarathy,Rajamalli, Pachaiyappan,Cheng, Chien-Hong
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supporting information
p. 4308 - 4311
(2016/04/01)
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