- Bi-aryl analogues of salicylic acids: Design, synthesis and sar study to ameliorate endoplasmic reticulum stress
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Introduction: Endoplasmic reticulum (ER) stress condition is characterized as the accu-mulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphtha-lene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods: Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results: Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion: Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases.
- Kim, Ye Eun,Kim, Dong Hwan,Choi, Ami,Jang, Seoul,Jeong, Kwiwan,Kim, Young-Mi,Nam, Tae-Gyu
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p. 3593 - 3604
(2021/08/30)
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- Synthesis of Polysubstituted 2-Naphthols by Palladium-Catalyzed Intramolecular Arylation/Aromatization Cascade
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A palladium-catalyzed intramolecular α-arylation and defluorinative aromatization strategy for the synthesis of polysubstituted 2-naphthols is reported. With ortho-bromobenzyl-substituted α-fluoroketones as the substrates and palladium acetate/triphenylphosphine as the catalyst, this method features good functional group tolerance, readily available catalyst and starting materials, and high yields. The applications of the strategy are demonstrated by the synthesis of useful building blocks, such as naphtha[2,3-b]furan, naphthol AS-D, and ligands/catalysts. (Figure presented.).
- Cai, Jinhui,Hu, Xu-Dong,Liu, Wen-Bo,Wang, Zhen-Kai,Yao, Fei,Zhang, Yun-Hao
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supporting information
(2020/02/25)
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- A new acylhydrazine N'-(1,3 dimethylbutylene)-3-hydroxy-naphthohydrazide based fluorescent sensor for the detection of Ni2+
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In this paper, a novel hydrazide compound (N'-(1,3 dimethylbutylene)-3-hydroxy-naphthohydrazide) (BMH) was synthesized by a simple three-stage reaction and its chemical structure was confirmed by 1H NMR, 13C NMR and FTIR characterization. This compound was used as fluorescent sensor for the detection of Ni2+ based on photoluminescence quenching. The fluorescence quenching of BMH upon the addition of Ni2+ is due to the formation of coordination complex which was verified by bind model and density functional theory studies. The Ni2+ concentration dependent fluorescence quenching efficiency of BMH was examined and the detection conditions were optimized. There is a good linear relationship between the emission intensity quenching (ΔF = F0–F) and the Ni2+ concentration (c) between 80 nM and 2 μM and the detection limit is 60 nM. The simple preparation of the compound BMH and the high sensitivity of the fluorescent sensor hold great promise for the determination of Ni2+ in environment.
- Duan, Abing,Li, Junhua,Liu, Mengqin,Luo, Chunhua,Peng, Hui,Tan, Yuxing,Yin, Zipeng
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- Overcoming the Deallylation Problem: Palladium(II)-Catalyzed Chemo-, Regio-, and Stereoselective Allylic Oxidation of Aryl Allyl Ether, Amine, and Amino Acids
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We report herein a Pd(II)/bis-sulfoxide-catalyzed intramolecular allylic C-H acetoxylation of aryl allyl ether, amine, and amino acids with the retention of a labile allyl moiety. Mechanistically, the reaction proceeds through a distinct double-bond isomerization from the allylic to the vinylic position followed by intramolecular carboxypalladation and the β-hydride elimination pathway. For the first time, C-H oxidation of N-allyl-protected amino acids to furnish five-membered heterocycles through 1,3-syn-addition is established with excellent diastereoselectivity.
- Begam, Hasina Mamataj,Jana, Ranjan,Manna, Kartic,Samanta, Krishanu
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supporting information
p. 7443 - 7449
(2020/10/09)
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- De Novo Synthesis of Phenols and Naphthols through Oxidative Cycloaromatization of Dienynes
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In this work, a rhodium-catalyzed oxidative cycloaromatization of dienynes, which provides a highly straightforward and efficient way to access polysubstituted naphthols and phenols under mild conditions, is described. Challenged electron-withdrawing groups are well tolerated in this protocol, and late-stage phenyl ring formation is demonstrated.
- Rong, Ming-Guang,Qin, Tian-Zhu,Liu, Xin-Rui,Wang, Hong-Fa,Zi, Weiwei
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supporting information
p. 6289 - 6293
(2018/10/09)
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- Hauser-Heck: Efficient Synthesis of γ-Aryl-β-ketoesters en Route to Substituted Naphthalenes
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γ-Aryl-β-ketoesters can be prepared in one step from aryl bromides and bis(trimethylsilyl) enol ethers using catalytic amounts of Pd(dba)2/t-Bu3P and stoichiometric amounts of Bu3SnF. The wide range of γ-(hetero)aryl-β-ketoesters that can be obtained illustrate the scope and limitations of this novel Hauser-Heck combination. γ-Aryl-β-ketoesters with a 1,3-dioxane acetal in the ortho position can easily be transformed into the hydroxy naphthoate in very good yield. Aqueous formic acid at 65 °C provides optimal conditions for this deprotective aromatization.
- Wagner, Frederic,Harms, Klaus,Koert, Ulrich
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supporting information
p. 5670 - 5673
(2015/12/08)
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- Synthesis and evaluation of an O-Aminated naphthol AS-E as a prodrug of CREB-mediated gene transcription inhibition
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An O-Aminated naphthol AS-E was designed as a prodrug to achieve reductive activation and improved aqueous solubility. During the synthesis of this designed compound, a novel transformation from aryl triflates and ethyl acetohydroximate to oxazoles was discovered. Although the initially designed O-Amino naphthol AS-E was not made successfully, the eventually synthesized O-tert-butylamino derivative was found to be biologically inactive, suggesting that reductive N-O cleavage in this compound was not facile due to unfavorable steric and electronic effects.
- Xie, Fuchun,Li, Bingbing X.,Xiao, Xiangshu
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p. 380 - 384
(2013/07/26)
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- Ruthenium(II)-catalyzed synthesis of hydroxylated arenes with ester as an effective directing group
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An unprecedented Ru(II) catalyzed ortho-hydroxylation has been developed for the facile synthesis of a variety of multifunctionalized arenes from easily accessible ethyl benzoates with ester as an efficient directing group. Both the TFA/TFAA cosolvent system and oxidants serve as the critical success factors in this transformation. The reaction demonstrates excellent reactivity, good functional group tolerance, and high yields.
- Yang, Yiqing,Lin, Yun,Rao, Yu
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supporting information; experimental part
p. 2874 - 2877
(2012/07/28)
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- Chemoselective esterification of phenolic acids in the presence of sodium bicarbonate in ionic liquids
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Chemoselective esterification of phenolic acids with dialkyl sulphates or alkyl halides in the presence of sodium bicarbonate in 1,3-dialkylimidazolium ionic liquids is reported in excellent yields and less reaction time as compared to organic solvents. Copyright Taylor & Francis Group, LLC.
- Ambika,Singh, Pradeep Pratap,Chauhan
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p. 928 - 936
(2008/09/17)
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- Novel potent 5-HT3 receptor ligands based on the pyrrolidone structure: Synthesis, biological evaluation, and computational rationalization of the ligand-receptor interaction modalities
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Novel conformationally constrained derivatives of classical 5-HT3 receptor antagonists were designed and synthesized with the aim of probing the central 5-HT3 receptor recognition site in a systematic way. The newly-synthesized compo
- Cappelli, Andrea,Anzini, Maurizio,Vomero, Salvatore,Mennuni, Laura,Makovec, Francesco,Doucet, Edith,Hamon, Michel,Menziani,De Benedetti, Pier G.,Giorgi, Gianluca,Ghelardini, Carla,Collina, Simona
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p. 779 - 801
(2007/10/03)
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- Naphthothietes and Their Application to the Synthesis of Heterocycles
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The three isomeric naphthothietes 5, 11, and 16 were prepared according to the reaction sequences shown in Schemes 1-3.The final step was in each case a flash vacuum pyrolysis (FVP) of the corresconding mercaptonaphthalenemethanol 4, 9, and 15, respectively.The thiete rings in 5 and 11 can be opened by gentle heating; the ring opening of the isomer 16 possesses a much higher activation barrier.A MNDO calculation of the ΔHf values of 5, 11, and 16 and the open isomers 5', 11', and 16' provides an explanation for the different behavior.Photochemical ring opening represents a useful alternative.The reaction Schemes 4, 6, and 7 reveal the synthetic potential of the naphtho-condensed thietes.Cycloaddition reactions with CC, CO, or CN double bonds lead into the series of differently condensed thiopyrans 17, 18, 24, 25, 26, 3,1-oxathiine 19 and 1,3-thiazines 20, 21. - Keywords: Naphthothietes; Flash vacuum pyrolysis; Hetero Diels-Alder reaction
- Mayer, Axel,Rumpf, Norbert,Meier, Herbert
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p. 2221 - 2226
(2007/10/03)
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- Stereognostic coordination chemistry. 1. The design and synthesis of chelators for the uranyl ion
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A new approach to the molecular recognition of metal oxo cations is introduced based on a ligand design strategy that provides at least one hydrogen bond donor for interaction with oxo group(s) as well as conventional electron pair donor ligands for coord
- Franczyk, Thaddeus S.,Czerwinski, Kenneth R.,Raymond, Kenneth N.
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p. 8138 - 8146
(2007/10/02)
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