- Triphenylphosphine/1,2-Diiodoethane-Promoted Formylation of Indoles with N, N -Dimethylformamide
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Despite intensive studies on the synthesis of 3-formylindoles, it is still highly desirable to develop efficient methods for the formylation of indoles, due to the shortcomings of the reported methods, such as inconvenient operations and/or harsh reaction conditions. Here, we describe a Ph3P/ICH2CH2I-promoted formylation of indoles with DMF under mild conditions. A Vilsmeier-type intermediate is readily formed from DMF promoted by the Ph3P/ICH2CH2I system. A onestep formylation process can be applied to various electron-rich indoles, but a hydrolysis needs to be carried out as a second step in the case of electron-deficient indoles. Convenient operations make this protocol attractive.
- Zhu, Yu-Rong,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 259 - 263
(2021/11/22)
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- Recyclable and reusablen-Bu4NBF4/PEG-400/H2O system for electrochemical C-3 formylation of indoles with Me3N as a carbonyl source
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A safe, practical and eco-friendly electrochemical methodology for the synthesis of 3-formylated indoles has been developed by the utilization of Me3N as a novel formylating reagent. Stoichiometric oxidants, metal catalysts, and activating agents were avoided in this method, and an aqueous biphasic system ofn-Bu4NBF4/PEG-400/H2O was used as a recyclable and reusable reaction medium, which made this electrosynthesis approach more sustainable and environmentally friendly. This process expanded the substrate scope and functional group tolerance for bothN-EDG andN-EWG indoles. Furthermore, late-stage functionalization and total/formal synthesis of drugs and natural products were realized by means of this route.
- Cheng, Didi,Li, Jingyi,Li, Yujin,Ling, Fei,Liu, Lei,Liu, Tao,Zhong, Weihui
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supporting information
p. 4107 - 4113
(2021/06/17)
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- First discovery of pimprinine derivatives and analogs as novel potential herbicidal, insecticidal and nematicidal agents
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Pimprinine and streptochlorin are indole natural products produced by many species of organisms, and they are reported to possess a wide range of biological activities, such as anticancer, antiviral, antifungal activity and so on. In this study, three series of pimprinine derivatives or analogs were efficiently synthesized under the optimized methods. Biological assays conducted at Syngenta firstly indicated the pimprinine derivatives or analogs possessed potential herbicidal and insecticidal activity, and this is highlighted by compounds 21g, 21h, 21i, 21j, 21l, 22h, 22i and 23h, they possessed significant biological activity as well as broad spectrum. Meanwhile, compounds with benzothiophene-oxazole core (21h, 22h and 23h), showed effective nematicidal activity in primary screening. Compounds 21g and 21i were identified as the most promising lead structures for further study.
- Zhang, Ming-Zhi,Mulholland, Nick,Seville, Anne,Hough, Gemma,Smith, Nicholas,Dong, Hong-Qiang,Zhang, Wei-Hua,Gu, Yu-Cheng
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supporting information
(2020/12/21)
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- Streptochlorin analogues as potential antifungal agents: Design, synthesis, antifungal activity and molecular docking study
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Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are re
- Gao, Ya,Huang, Dai-Chuan,Liu, Chang,Song, Zi-Long,Liu, Jing-Rui,Guo, Shu-Ke,Tan, Jun-Yang,Qiu, Run-Ling,Jin, Bing,Zhang, Haifeng,Mulholland, Nick,Han, Xinya,Xia, Qinfei,Ali, Abdallah S.,Guo, Dale,Deng, Yun,Gu, Yu-Cheng,Zhang, Ming-Zhi
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- Synthesis, Characterization, and Antioxidant Properties of Novel 1-(4-Aryl-1,3-thiazol-2-yl)-2-{[1-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methylidene}hydrazines
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Abstract: A series of novel 1-(4-aryl-1,3-thiazol-2-yl)-2-{[1-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyli-dene}hydrazines were synthesized and properly characterized through IR, 1H and 13C NMR, and HRMS spectroscopic techniques. The synthesized compounds were screened for their antioxidant properties by using DPPH radical scavenging assay in comparison to ascorbic acid used as standard. The presence of a prenyl chain makes those compounds more lipophilic, which plays a crucial role in their radical scavenging activity. 1-{5-Bromo-[1-(3-methylbut-2-enyl)-1H-indole-3-yl]methylidene}-2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hy-dra-zine showed a promising antioxidant activity.
- Durgeswari, L. K.,Ganta, Ravi Kumar,Murthy, Y. L. N.
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p. 1552 - 1558
(2021/10/26)
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- Cu(II) complexes of 2-indole thiocarbohydrazones: synthesis, characterization and DNA cleavage studies
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Abstract: Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. FT1 crystallizes in the triclinic system while FT2 in the orthorhombic. The DNA cleavage activity of Cu(II) complexes was studied using plasmid pBR322 DNA by gel electrophoresis. All compounds cleave DNA on photoirradiation by oxidative mechanism. Graphic abstract: Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. Both the Cu(II) complexes of indole thiocarbohydrazones are shown to cleave plasmid pBR322 DNA by oxidative mechanism.[Figure not available: see fulltext.].
- Amate, Anita,Butcher, Raymond J,Chakravarty, Debamitra,Kumbhar, Anupa A,Pawar, Shridhar
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- Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity
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Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.
- Nimbarte, Vijaykumar D.,Wirmer-Bartoschek, Julia,Gande, Santosh L.,Alshamleh, Islam,Seibert, Marcel,Nasiri, Hamid Reza,Schnütgen, Frank,Serve, Hubert,Schwalbe, Harald
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p. 1667 - 1679
(2021/03/24)
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- Design, synthesis, anticancer activity, molecular docking and ADME studies of novel methylsulfonyl indole-benzimidazoles in comparison with ethylsulfonyl counterparts
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Cancer poses a world-wide healthcare problem, demanding selective and effective therapy protocols. To address that, a vast amount of therapeutic candidates are being investigated in the field of medicinal chemistry. Accordingly, indole-benzimidazole structures have recently gained considerable interest because of their anticancer properties and estrogen receptor (ER) modulatory actions. In this study, novel methylsulfonyl indole-benzimidazole derivatives have been synthesized upon substitution of respectively the first (R1) and fifth (R2) positions of benzimidazole and indole groups. Structure and activity relationships were then studied via1H NMR, 13C NMR, mass spectral and in silico docking analyses, as well as cell viability measurements. We found that the compounds exhibited substantial affinity levels towards ER alpha (ERα). In addition, the correlation analysis of cytotoxicity profiles between ethyl- and methyl-sulfonyl indole-benzimidazoles revealed a collection of effective and consistent R1 and R2 substitutions. However, for some candidate derivatives, distinctive cytotoxicity levels and varying viability versus ERα affinity correlations were observable across the studies, suggesting that the sulfonyl side chain modifications themselves can also influence the ERα binding levels. These results demonstrated that our novel methylsulfonyl indole-benzimidazole derivatives, similar to their ethylsulfonyl counterparts, exhibit anticancer effects with potential estrogen receptor modulatory actions. This journal is
- Karadayi, Fikriye Zengin,Yaman, Murat,Kisla, Mehmet Murat,Konu, Ozlen,Ates-Alagoz, Zeynep
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p. 9010 - 9019
(2021/06/06)
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- Anti-leukemic properties of aplysinopsin derivative ee-84 alone and combined to bh3 mimetic a-1210477
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Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski’s rule of five. Furthermore, EE-84 induced a senescent-like phenotype in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells underwent morphological changes in line with mitochondrial dysfunction concomitant with autophagy and ER stress induction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor A-1210477, against imatinib-sensitive and resistant K562 cells, highlighting the inhibition of antiapoptotic Bcl-2 proteins as a promising novel senolytic approach against chronic myeloid leukemia.
- Song, Sungmi,Kim, Sua,El-Sawy, Eslam R.,Cerella, Claudia,Orlikova-Boyer, Barbora,Kirsch, Gilbert,Christov, Christo,Dicato, Mario,Diederich, Marc
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- N-skatyltryptamines-dual 5-ht6r/d2r ligands with antipsychotic and procognitive potential
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A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, and D2 receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D2 receptor antagonists with additional 5-HT6R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT6R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT6R agonists was more ambiguous-in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D2R antagonist function combined with 5-HT6R agonism, and mixed D2/5-HT6R antagonists in murine models of psychosis.
- Bojarski, Andrzej J.,Bugno, Ryszard,Cie?lik, Paulina,Duszyńska, Beata,Handzlik, Jadwiga,Hogendorf, Adam S.,Hogendorf, Agata,Kaczorowska, Katarzyna,Kurczab, Rafa?,Latacz, Gniewomir,Lenda, Tomasz,Sata?a, Grzegorz,Staroń, Jakub,Szewczyk, Bernadeta
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- Nickel catalyzed hydrosilane reduction of (het)arenecarboxylic acids into aldehydes
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Nickel-catalyzed reduction of (het)arenecarboxylic acids with hydrosilanes in the presence of dimethyl dicarbonate as the activator affords the corresponding aldehydes. The role of the activator is the conversion of the acids into their anhydrides undergoing C–O cleavage. The good yields were achieved in case of substrates bearing electron-donating and electron-neutral groups.
- Wang, Liang,Wang, Yaoyao,Tao, Yu,Zhang, Nana,Li, Shubai
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p. 271 - 273
(2021/05/04)
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- A TEMPO-Functionalized Ordered Mesoporous Polymer as a Highly Active and Reusable Organocatalyst
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The properties of high stability, periodic porosity, and tunable nature of ordered mesoporous polymers make these materials ideal catalytic nanoreactors. However, their application in organocatalysis has been rarely explored. We report herein for the first time the incorporation of a versatile organocatalyst, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), into the pores of an FDU-type mesoporous polymer via a pore surface engineering strategy. The resulting FDU-15-TEMPO possesses a highly ordered mesoporous organic framework and enhanced stability, and shows excellent catalytic activity in the selective oxidation of alcohols and aerobic oxidative synthesis of 2-substituted benzoxazoles, benzimidazoles and benzothiazoles. Moreover, the catalyst can be easily recovered and reused for up to 7 consecutive cycles.
- Guo, Ying,Wang, Wei David,Li, Shengyu,Zhu, Yin,Wang, Xiaoyu,Liu, Xiao,Zhang, Yuan
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supporting information
p. 3689 - 3694
(2021/09/29)
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- Hierarchical CeO2@N-C Ultrathin Nanosheets for Efficient Selective Oxidation of Benzylic Alcohols in Water
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A monodisperse CeO2@N-C ultrathin nanosheet self-assembled hierarchical structure (USHR) has been prepared by metal-organic framework template methods. The uniform coating of nitrogen-doped carbon (N-C) layers could play an important role in the adsorption and activation of benzylic alcohol. The unique 3D hierarchical structure self-assembled by ultrathin nanosheets provided enough active sites for the catalytic reaction. Therefore, the CeO2@N-C USHR can afford excellent catalytic performance for selective oxidation of benzylic alcohols in water.
- Han, Xiguang,Hao, Juan,Long, Zhouyang,Sun, Liming,Wang, Xiaojun,Zhan, Wenwen
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supporting information
p. 7732 - 7737
(2021/06/27)
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- Molecular iodine mediated oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups into aldehydes
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The oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups is achieved by employing molecular iodine as a mild oxidizing agent under ambient conditions in the presence of a mild base. The important reaction of C3 formylation of free NH and substituted indoles containing various substituents is accomplished from the corresponding Mannich bases. This methodology can also be extended for the synthesis of aryl and other heteroaryl aldehydes and ketones. Furthermore, the usefulness of the method is successfully demonstrated on a gram scale.
- Mandrekar, Ketan S.,Tilve, Santosh G.
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supporting information
p. 4152 - 4155
(2021/03/15)
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- Photo-on-Demand Synthesis of Vilsmeier Reagents with Chloroform and Their Applications to One-Pot Organic Syntheses
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The Vilsmeier reagent (VR), first reported a century ago, is a versatile reagent in a variety of organic reactions. It is used extensively in formylation reactions. However, the synthesis of VR generally requires highly toxic and corrosive reagents such as POCl3, SOCl2, or COCl2. In this study, we found that VR is readily obtained from a CHCl3 solution containing N,N-dimethylformamide or N,N-dimethylacetamide upon photo-irradiation under O2 bubbling. The corresponding Vilsmeier reagents were obtained in high yields with the generation of gaseous HCl and CO2 as byproducts to allow their isolations as crystalline solid products amenable to analysis by X-ray crystallography. With the advantage of using CHCl3, which bifunctionally serves as a reactant and a solvent, this photo-on-demand VR synthesis is available for one-pot syntheses of aldehydes, acid chlorides, formates, ketones, esters, and amides.
- Liang, Fengying,Eda, Kazuo,Okazoe, Takashi,Wada, Akihiro,Mori, Nobuaki,Konishi, Katsuhiko,Tsuda, Akihiko
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p. 6504 - 6517
(2021/05/06)
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- C3-Formylation of Indoles in Continuous Flow
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We have developed a continuous flow C3-formylation technique for indoles using hexamethylenetetramine (HMTA) and iodine. A mixed solvent system of DMF–H2O (1:1, vol/vol) completely dissolves reagents and prevents clogging of microchannels during fluid flow. The continuous flow technique provides maximized mixing and excellent heat transfer efficiency. Thus, flow chemistry accelerates the rate of C3-formylation of indoles in the absence of a strong acid, base, or metal catalyst. We show that high yields of C3-formylated indoles (up to 83%) can be obtained at 150°C when the residence time is as low as 8 min.
- Sung, Ha Kyoung,Kim, Dong Hyun,Kim, Joon Seok,Park, Chan Pil
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supporting information
p. 388 - 392
(2020/12/30)
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- Preparation method and application of natural product Streptochlorin and derivatives thereof
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The invention discloses a preparation method of a derivative of a natural product Streptochlorin. The invention also discloses an application of the natural product Streptochlorin and the derivative thereof in killing pathogenic bacteria of crops. The natural product Streptochlorin and the derivative thereof have the advantages that the bactericidal activity is good, can be applied to crop diseases caused by fungi, bacteria and viruses, and show efficient and/or broad-spectrum bactericidal activity.
- -
-
Paragraph 0063-0068
(2020/07/12)
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- Anti-tumor compound NY and series of derivatives thereof
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The invention relates to an anti-tumor compound NY and a series of derivatives thereof, and an application of the anti-tumor compound NY and the series of derivatives of the anti-tumor compound NY inmedicines. According to the invention, ADAM17 is used as a target spot to design and completely synthesize 15 compounds of NY series; and the antitumor activity of the 15 compounds of the NY series isverified; thus, a potential antitumor activity drug is provided clinically.
- -
-
Paragraph 0058-0061
(2020/05/02)
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- Nitrile Synthesis by Aerobic Oxidation of Primary Amines and in situ Generated Imines from Aldehydes and Ammonium Salt with Grubbs Catalyst
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Herein, a Grubbs-catalyzed route for the synthesis of nitriles via the aerobic oxidation of primary amines is reported. This reaction accommodates a variety of substrates, including simple primary amines, sterically hindered β,β-disubstituted amines, allylamine, benzylamines, and α-amino esters. Reaction compatibility with various functionalities is also noted, particularly with alkenes, alkynes, halogens, esters, silyl ethers, and free hydroxyl groups. The nitriles were also synthesized via the oxidation of imines generated from aldehydes and NH4OAc in situ. (Figure presented.).
- Utsumi, Tatsuki,Noda, Kenta,Kawauchi, Daichi,Ueda, Hirofumi,Tokuyama, Hidetoshi
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supporting information
p. 3583 - 3588
(2020/08/05)
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- Design, synthesis, and biological evaluation of sorafenib derivatives containing indole (ketone) semicarbazide analogs as antitumor agents
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A series of new sorafenib derivatives was designed and synthesized. The antiproliferative activity of the synthesized compounds against human lung cancer cell (A549), human pancreatic cancer cell (PC-3), human leukemia cell (K562), and human hepatoma cell (SMMC-7721) was evaluated by MTT assay. The results revealed that several compounds displayed more significant antitumor activities than commercial anticancer agent sorafenib against SMMC-7721. In addition, compounds 7a, 7g, 7l, 7m, and 7p represented obvious growth inhibition with IC50 values of 1-9 μM against four cancer cell lines, demonstrating more predominant activities against cancer cells as compared to sorafenib. Furthermore, some structure-activity relationships have also been established. Compounds containing indole and benzene ring substituted by halogen showed better activity than sorafenib. Wound healing assay suggested that cells would be targeted on their migratory capacity by 7g, potentially affecting the migration activity of these tumors. The effects of A549 and PC-3 cell apoptosis induced by compound 7g were significantly increased compared with sorafenib. Importantly, the result of western blot assay showed that 7g inhibited cell growth by suppressing the activity of EGFR, especially the expression of p-EGFR (Tyr1068).
- Li, Wen,Qi, Ya-Yun,Wang, Yuan-Yuan,Gan, Yi-Yuan,Shao, Li-Hui,Zhang, Li-Qiong,Tang, Zhen-Hua,Zhu, Mei,Tang, Si-Yu,Wang, Zhen-Chao,Ouyang, Gui-Ping
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p. 2548 - 2560
(2020/04/02)
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- Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
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We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
- Aleku, Godwin A.,Leys, David,Roberts, George W.
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supporting information
p. 3927 - 3939
(2020/07/09)
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- FeCl3-catalyzed oxidative decarboxylation of aryl/heteroaryl acetic acids: Preparation of selected API impurities
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There is an ever-increasing demand for impurity compounds for use in impurity profiling as regulatory agencies seek information during registration. Herein, we report the FeCl3-catalyzed oxidative decarboxylation of aryl- and heteroaryl acetic acids to the corresponding carbonyl compounds. A variety of useful aldehydes and ketones were prepared in a simple one-pot transformation by employing an environmentally benign, low-cost, and readily available iron salt. The utility of this method has been demonstrated by preparing five valuable API impurities including a multi-gram-scale synthesis of ketorolac impurity B for the first time. This journal is
- Gangadurai, Chinnakuzhanthai,Illa, Giri Teja,Reddy, D. Srinivasa
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p. 8459 - 8466
(2020/11/05)
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- Visible-light mediated facile dithiane deprotection under metal free conditions
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Visible light mediated facile and selective dithiane deprotection under metal free conditions is developed. Eosin Y (1 mol%) proved to be an effective catalyst for the dithiane deprotection under the ambient photoredox conditions. The standard household compact fluorescent light source (CFL bulb) proved to be effective under open-air conditions in aqueous acetonitrile at room temperature. The protocol that exhibits a broad substrate scope and functional group tolerance has been shown to expand to a range of transformations for the electron-rich and -deficient thioacetals and thioketals. The synthetic utility of this protocol has also been demonstrated by gram-scale application.
- Dharpure, Pankaj D.,Bhowmick, Anindita,Warghude, Prakash K.,Bhat, Ramakrishna G.
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- Screening metal-free photocatalysts from isomorphic covalent organic frameworks for the C-3 functionalization of indoles
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The visible-light-driven organic transformation using two-dimensional covalent organic frameworks (2D-COFs) as metal-free heterogeneous photocatalysts is a green and sustainable approach, and it has gained a surge of interest by virtue of the photosensitizer's high crystallinity, abundant porosity, outstanding stability, excellent light-harvesting ability and tunable structure. However, the guiding principle for designing, constructing and selecting COF-based photocatalysts has not been put forward so far. Herein, we contribute a fascinating strategy to guide the acquisition of excellent framework photocatalysts, which is to screen them from a series of isomorphic COFs. As a proof of concept, three new isomorphic pyrene-based 2D-COFs (COF-JLU23, COF-JLU24 and COF-JLU25) with variable linkers were successfully synthesized. In addition to having similar crystallinity and porosity with the same pore size and shape, their absorption, emission, bandgap, energy level, transient photocurrent response and photocatalytic activity could be easily adjustedviaconfiguring different linkers in frameworks. Indeed, COF-JLU24 with electron donor-acceptor characteristics exhibited the best photocatalytic activity among the three isomorphic COFs for C-3 functionalization reactions of indoles, even better than that of the metal-free photocatalyst g-C3N4. More importantly, the screened COF-JLU24 as a metal-free photocatalyst still displayed extensive substrate adaptability and excellent recyclability. We anticipate that this strategy will become a robust rule of thumb for fast access to COF-based photocatalysts. In addition, we still highlight that the present study broadens the applied frontier of COF-based photocatalysts.
- Chen, Xiong,Feng, Xiao,Han, Songjie,Li, Chunzhi,Li, He,Li, Ziping,Liu, Xiaoming,Shao, Pengpeng,Xia, Hong
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supporting information
p. 8706 - 8715
(2020/05/16)
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- A NaH-promoted N-detosylation reaction of diverse p-toluenesulfonamides
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A NaH-mediated detosylation reaction of various Ts-protected indoles, azaheterocycles, anilines and dibenzylamine was reported. The method features cheap reagent, convenient operations, mild reaction conditions and broad substrate scope. Moreover, this study revealed that the loading of NaH in tosylation reactions of nitrogen-containing compounds with NaH as a base in DMA or DMF should be controlled due to the possibility of adverse detosylation.
- Sun, Wanwan,Chen, Xiaobei,Hu, Ying,Geng, Huihui,Jiang, Yuanrui,Zhou, Yuxin,Zhu, Wenjing,Hu, Min,Hu, Haohua,Wang, Xingyi,Wang, Xinli,Zhang, Shilei,Hu, Yanwei
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supporting information
(2020/10/05)
-
- Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors
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Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.
- Liu, Hong-Min,Suo, Feng-Zhi,Li, Xiao-Bo,You, Ying-Hua,Lv, Chun-Tao,Zheng, Chen-Xing,Zhang, Guo-Chen,Liu, Yue-Jiao,Kang, Wen-Ting,Zheng, Yi-Chao,Xu, Hai-Wei
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p. 357 - 372
(2019/05/17)
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- Synthesis of an azide-tethered 4H-furo[3,4-b]indole
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We describe the synthesis of a novel azide-tethered 4H-furo[3,4-b]indole as a putative intermediate for a projected route to the 2-acylindole class of indole alkaloids. O N3 Me N N N H N H H O
- Keavy, Daniel J.,Liu, Yanbing,Gribble, Gordon W.
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p. 368 - 375
(2020/02/13)
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- Potassium-ion competitive acid blocker containing indole structure and preparation method and application of potassium-ion competitive acid blocker
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The invention discloses an indole derivative or a pharmaceutically acceptable salt thereof and particularly relates to a compound containing a 1-sulfonyl-3-alkylamino methyl indole structure. The compound is shown as a formula I. The invention also discloses a preparation method of the indole derivative and application of the indole derivative in preparation of a potassium-ion competitive acid blocker or a drug for treating acid-related diseases. The preparation method has the advantages of being simple and high in yield and reproducibility.
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-
Paragraph 0051; 0053-0055
(2019/07/08)
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- Synthesis, characterization, and biological evaluation of indole aldehydes containing N-benzyl moiety
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The present study describes the synthesis, characterization and biological evaluation of N-benzyl indole aldehydes. The biological activities of the newly synthesized compounds were examined by investigating their antioxidant and anti-inflammatory activities. The potential of these compounds as an antioxidant was determined by 2,2-diphenylpicrylhydrazyl, Nitric oxide, Superoxide, peroxide radical scavenging methods. We found that aldehydes 4a, 4b, 4c, and 4e and shows promising in vitro DPPH scavenging antioxidant activity while aldehyde 4b and 4e show good in vitro anti-inflammatory activity.
- Survase, Dattatray N.,Karhale, Shrikrishna S.,Khedkar, Vijay M.,Helavi, Vasant B.
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p. 3486 - 3497
(2019/11/11)
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- A [3,3] sigmatropic and novel ipso [3,3] sigmatropic rearrangement of 1-hydroxyindole chemistry
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Utilizing 1-aryloxyindole derivatives, we found a new type of [3,3] sigmatropic rearrangement reaction. We named it as ipso [3,3] sigmatropic rearrangement. The product structures are strictly determined by X-ray crystallographic analysis. Normal [3,3] sigmatropic rearrangement of 1-hydroxyindole derivative was found to be a useful synthetic method for 2H-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione derivative.
- Fukui, Yoshikazu,Kobayashi, Tetsuya,Kawasaki, Toshiya,Yamada, Fumio,Somei, Masanori
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p. 465 - 483
(2019/08/02)
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- Preparation of large-size, superparamagnetic, and highly magnetic Fe3O4@PDA core-shell submicrosphere-supported nano-palladium catalyst and its application to aldehyde preparation through oxidative dehydrogenation of benzyl alcohols
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Large-size, superparamagnetic, and highly magnetic Fe3O4@PDA core-shell submicrospheresupported nano-palladium catalysts were prepared in this study. Dopamine was encapsulated on the surface of Fe3O4 particles via self-polymerization and then protonated to positively charge the microspheres. PdCl42- was dispersed on the surface of the microspheres by positive and negative charge attraction and then reduced to nano-palladium. With air as oxidant, the catalyst can successfully catalyze the dehydrogenation of benzyl alcohols to produce the corresponding aldehydes at 120 °C.
- Guo, Haichang,Zheng, Renhua,Jiang, Huajiang,Xu, Zhenyuan,Xia, Aibao
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- Synthesis, antiproliferative and apoptosis induction potential activities of novel bis(indolyl)hydrazide-hydrazone derivatives
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In recent years, indole-indazolyl hydrazide-hydrazone derivatives with strong cell growth inhibition and apoptosis induction characteristics are being strongly screened for their cancer chemo-preventive potential. In the present study, N-methyl and N,N-dimethyl bis(indolyl)hydrazide-hydrazone analog derivatives were designed, synthesized and allowed to evaluate for their anti-proliferative and apoptosis induction potential against cervical (HeLa), breast (MCF-7 and MDA-MB-231) and lung (A549) cancer cell lines relative to normal HEK293 cells. The MTT assay in conjunction with mitochondrial potential assays and the trypan blue dye exclusion were employed to ascertain the effects of the derivatives on the cancer cells. Further, mechanistic studies were conducted on compound 14a to understand the biochemical mechanisms and functional interactions with various signaling pathways triggered in HeLa and MCF-7 cells. Compound 14a induced apoptosis via caspase independent pathway through the participation of mitogen-activated protein kinases (MAPK) such as extracellular signal related kinase (ERK) and p38 as well as p53 pathways. It originates the activation of pro-apoptotic proteins such as Bak and Mcl-1s and also strongly induced the generation of reactive oxygen species. In downstream signaling pathway, activated p53 protein interacted with MAPK pathways, including SAPK/c-Jun N-terminal protein kinase (JNK), p38 and ERK kinases resulting in apoptotic cell death. The involvement of MAPK cascades such as p38, ERK and p38 on compound 14a induced apoptotic cell death was evidenced by the fact that the inclusion of specific inhibitors of p38, ERK1/2 and JNK MAPK (SB2035809, PD98059 and SP600125) prevented the compound 14a towards induced apoptosis. The results clearly showed that MAP kinase cascades were crucial for apoptotic response in compound 14a induced cellular killing and were dependent on p53 activity. Based on the results, compound 14a was identified as a promising candidate for cancer therapeutics and these findings furnish a basis for further in vivo experiments on anti-proliferative activity.
- Sreenivasulu, Reddymasu,Reddy, Kotthireddy Thirumal,Sujitha, Pombala,Kumar, C. Ganesh,Raju, Rudraraju Ramesh
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p. 1043 - 1055
(2019/02/19)
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- Synthesis of 3-Formylindoles via Electrochemical Decarboxylation of Glyoxylic Acid with an Amine as a Dual Function Organocatalyst
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A new method for 3-formalytion of indoles has been developed through electrochemical decarboxylation of glyoxylic acid with the amine as a dual function organocatalyst. The amine facilitated both the electrochemical decarboxylation and the nucleophilic reaction efficiently, whose loading can be as low as 1 mol %. This protocol has a broad range of functional group tolerance under ambient conditions. The gram-scale experiment has shown great potential in the synthetic application of this strategy.
- Lin, Dian-Zhao,Huang, Jing-Mei
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supporting information
p. 5862 - 5866
(2019/08/26)
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- Selective C-H acylation of indoles with α-oxocarboxylic acids at the C4 position by palladium catalysis
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The first Pd-catalyzed direct C-H acylation of indoles at the C4 position with α-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of α-oxocarboxylic acids and the involvement of a PdII/PdIV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors.
- Zhang, Jitan,Wu, Manyi,Fan, Jian,Xu, Qiaoqiao,Xie, Meihua
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supporting information
p. 8102 - 8105
(2019/07/15)
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- Electrochemically Enabled C3-Formylation and -Acylation of Indoles with Aldehydes
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Reported herein is an effective strategy for oxidative cross-coupling of indoles with various aldehydes. The strategy is based on a two-step transformation via a well-known Mannich-type reaction and a C-N bond cleavage for carbonyl introduction. The key step - the C-N bond cleavage of the Mannich product - was enabled by electrochemistry. This strategy (with over 40 examples) ensures excellent functional-group tolerance as well as late-stage functionalization of pharmaceutical molecules.
- Yang, Liquan,Liu, Zhaoran,Li, Yujun,Lei, Ning,Shen, Yanling,Zheng, Ke
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supporting information
p. 7702 - 7707
(2019/10/19)
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- Coenzyme A-Conjugated Cinnamic Acids – Enzymatic Synthesis of a CoA-Ester Library and Application in Biocatalytic Cascades to Vanillin Derivatives
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We present a bioorthogonal method for the ligation of coenzyme A (CoA) with cinnamic acids. The reaction, which is the initial step in the biosynthesis of a multitude of bioactive secondary metabolites, is catalyzed by a promiscuous plant ligase and yields CoA conjugates with different functionalization in high purity and without formation of by-products. Its applicability in biosynthetic cascades is shown for the direct transformation of cinnamic acids into natural benzaldehydes (like vanillin) or artificial derivatives (e. g. ethylvanillin). (Figure presented.).
- Dippe, Martin,Bauer, Anne-Katrin,Porzel, Andrea,Funke, Evelyn,Müller, Anna O.,Schmidt, Jürgen,Beier, Maria,Wessjohann, Ludger A.
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supporting information
p. 5346 - 5350
(2019/11/29)
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- Synthesis and nonlinear optical properties of novel conjugated small molecules based on indole donor
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Buchwald-Hartwig amination of aryl halides with solvent-free condition was used for the preparation of electron donors with high density of electron cloud. Organic second order nonlinear optical chromophore ZML-c based on this electron donor was designed and synthesized. And chromophore ZML-ref without modified groups was also prepared as the contrast. Their delocalized energy levels were estimated by UV–Vis. spectra. Their thermal properties were studied by thermogravimetric analysis (TGA). Obviously, chromophore ZML-c showed lower delocalized energy levels and lower thermal decomposition temperature (just about 160 °C). The poled films showed the largest electro-optic (EO) coefficients of 23.5 pm/V and 10.6 pm/V respectively for chromophore ZML-c and ZML-ref. These results indicate that effective modification in indole ring may be a promising way to drastically change the electro-optical features of the titled compounds and show a direction of designing new electron donor in the field of nonlinear optical materials.
- Liu, Jialei,Zhang, Maolin,Gao, Wu,Fedorchuk,Kityk
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p. 223 - 227
(2018/05/29)
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- Synthesis of Camalexin and Related Analogues
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Camalexin is synthesized on a gram scale by coupling of thiazole and indole in an amidoalkylation–oxidation sequence. Several high-yielding implementations of this two-step approach are demonstrated with variation of either the intermediate acyliminium reagent or the oxidation conditions. Benzo-analogues and aza-analogues of the natural product are also obtained by this method. As a side result, a new formylation of indole is demonstrated.
- Stremski, Yordan,Statkova-Abeghe, Stela,Angelov, Plamen,Ivanov, Iliyan
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p. 1589 - 1595
(2018/07/25)
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- Beta- tetrahydro-carboline antifungal drug and preparation method and application thereof
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The invention discloses a beta-tetrahydro-carboline antifungal compound and a pharmaceutically acceptable salt thereof. The structure of the compound is shown as the general formula I, wherein n is 1to 3; R1 is hydrogen or monosubstituted acetylene or polysubstituted acetylene in any optional position on the benzene ring, X is O or NH, R2 is substituted or unsubstituted aliphatic or aromatic ring; or X is NR3, R2 and R3 are individually lower alkyl and substituted or unsubstituted aliphatic or aromatic ring; or X is N, R2 and X composes substituted or unsubstituted heterocycloalkyl. The invention also discloses a preparation method of the compound and the application of the compound in preparation of antifungal drugs. The compound has the characteristic of well antifungal activity, the result of partial compound is better than that of the control drug fluconazole, and the compound can be utilized to prepare antifungal drugs. The experiment result also show that the combined usage of the partial compound and fluconazole has good synergistic effect to clinically isolated fluconazole-resistant candida albicans.
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Paragraph 0114; 0115; 0116; 0117
(2018/11/22)
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- Synthesis of structurally diverse biflavonoids
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Synthetic biflavonoids are associated with interesting biological activities, yet they remain poorly explored within drug discovery. Recent years have witnessed a growing interest in synthetic approaches that can provide access to structurally novel biflavonoids so that the biological usefulness of this compound class can be more fully investigated. Herein, we report upon the exploration of strategies based around Suzuki-Miyaura cross-coupling and alcohol methylenation for the synthesis of two classes of biflavonoids: (i) rare ‘hybrid’ derivatives containing flavonoid monomers belonging to different subclasses, and (ii) homodimeric compounds in which the two flavonoid monomers are linked by a methylenedioxy group. Application of these strategies enabled the preparation of a structurally diverse collection of novel biflavonoids from readily-available starting materials, thereby facilitating the probing of uncharted regions of biologically interesting chemical space.
- Sum, Tze Jing,Sum, Tze Han,Galloway, Warren R.J.D.,Twigg, David G.,Ciardiello, Joe J.,Spring, David R.
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supporting information
p. 5089 - 5101
(2018/05/23)
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- Design, synthesis, and molecular docking of novel indole scaffold-based VEGFR-2 inhibitors as targeted anticancer agents
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A series of new indole derivatives 1–18 was synthesized and tested for their cytotoxic activity on a panel of 60 tumor cell lines. Additionally, molecular docking was carried out to study their binding pattern and binding affinity in the VEGFR-2 active site using sorafenib as a reference VEGFR-2 inhibitor. Based on the molecular docking results, compounds 5a, 5b, 6, 7, 14b, 18b, and 18c were selected to be evaluated for their VEGFR-2 inhibitory activity. Compound 18b exhibited a broad-spectrum antiproliferative activity on 47 cell lines, with GI % ranging from 31 to 82.5%. Moreover, compound 18b was the most potent VEGFR-2 inhibitor with an IC50 value of 0.07 μM, which is more potent than that of sorafenib (0.09 μM). A molecular docking study attributed the promising activity of this series to their hydrophobic interaction with the VEGFR-2 binding site hydrophobic side chains and their hydrogen bonding interaction with the key amino acids Glu885 and/or Asp1046.
- Roaiah, Hanaa M.,Ghannam, Iman A. Y.,Ali, Islam H.,El Kerdawy, Ahmed M.,Ali, Mamdouh M.,Abbas, Safinaz E-S.,El-Nakkady, Sally S.
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- Selective nickel-catalyzed dehydrogenative-decarboxylative formylation of indoles with glyoxylic acid
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Herein we present a new strategy for the dehydrogenative-decarboxylative coupling of indoles with glyoxylic acid. A broad range of indoles were transformed into the corresponding 3-formylindoles in moderate to good yields and excellent functional group tolerance. Notably, no N-formylation product was detected under our conditions.
- Yin, Zhiping,Wang, Zechao,Wu, Xiao-Feng
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supporting information
p. 3707 - 3710
(2018/05/31)
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- An efficient and sustainable protocol for oxidation of alcohols to carbonyl compounds
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A simple and extremely efficient protocol is developed for oxidation of alcohols to carbonyl compounds at room temperature by using green solvent lactic acid and green oxidant H2O2. This protocol provides high conversion under catalyst free conditions. The easy work up procedure allows high selectivity and good to excellent yields of carbonyl compounds with purity. We have performed wide range of substrates in present study with primary focus on reusability of lactic acid.
- Wagh, Ravindra B.,Nagarkar, Jayashree M.
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supporting information
p. 3443 - 3447
(2018/08/20)
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- Metal-Free catalyst for visible-light-induced oxidation of unactivated alcohols using Air/Oxygen as an oxidant
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9-Fluorenone acts as a metal-free and additive-free photocatalyst for the selective oxidation of primary and secondary alcohols under visible light. With this photocatalyst, a plethora of alcohols such as aliphatic, heteroaromatic, aromatic, and alicyclic compounds has been converted to the corresponding carbonyl compounds using air/oxygen as an oxidant. In addition to these, several steroids have been oxidized to the corresponding carbonyl compounds. Detailed mechanistic studies have also been achieved to determine the role of the oxidant and the photocatalyst for this oxidation.
- Schilling, Waldemar,Riemer, Daniel,Zhang, Yu,Hatami, Nareh,Das, Shoubhik
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p. 5425 - 5430
(2018/05/15)
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- Pseudohalide assisted aerobic oxidation of alcohols in the presence of visible-light
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Pseudohalides are well known to do similar chemistry like halides. Thiocyanate, a pseudohalide acts like halides in many ways. Thiocyanate radicals ([rad]SCN) are generated from readily available thiocyanate salts using Rose Bengal through single electron transfer (SET) in the presence of visible light. Thiocyanate radicals abstract hydrogen like other halide radicals, so this aspect of chemistry was used for the oxidation of alcohols to their corresponding aldehydes using oxygen as the terminal oxidant. This method shows a broad scope and well tolerance towards various functional groups.
- Sheriff Shah, Sk,Pradeep Singh
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supporting information
p. 247 - 251
(2018/01/03)
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- DNA-Templated [2+2] Photocycloaddition: A Straightforward Entry into the Aplysinopsin Family of Natural Products
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Biosynthetic considerations inspired us to harness the templating properties offered by DNA to promote a [2+2] photoinduced cycloaddition. The method was developed based on the dimerization of (E)-aplysinopsin, which was previously shown to be unproductive in solution. In sharp contrast, exposure of this tryptophan-derived olefin to light in the presence of salmon testes DNA (st-DNA) reproducibly afforded the corresponding homo-dimerized spiro-fused cyclobutane in excellent yields. DNA provides unique templating interactions enabling a singular mimic of the solid-state aggregation necessary for the [2+2] photocycloaddition to occur. This method was ultimately used to promote the prerequisite dimerizations leading to both dictazole B and tubastrindole B, thus constituting the first example of a DNA-mediated transformation to be applied to the total synthesis of a natural product.
- Duchemin, Nicolas,Skiredj, Adam,Mansot, Justine,Leblanc, Karine,Vasseur, Jean-Jacques,Beniddir, Mehdi A.,Evanno, Laurent,Poupon, Erwan,Smietana, Michael,Arseniyadis, Stellios
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supporting information
p. 11786 - 11791
(2018/09/10)
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- Rhodium(III)-Catalyzed Regioselective Direct C4-Alkylation and C2-Annulation of Indoles: Straightforward Access to Indolopyridone
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A straightforward RhIII-catalyzed strategy was developed for the site-selective C4-alkylation and C2-annulation of indole by using electronically variable diazo esters. The transformation was accomplished with the assist of an oxime directing group at the C3 position of the indole core with wide scope and functional-group tolerance. The method directly provided an indolopyridone core. The selectivity was triggered by the reactivity of the diazo coupling partner.
- Biswas, Aniruddha,Samanta, Rajarshi
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p. 1426 - 1436
(2018/04/06)
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- Chemical structures of novel maillard reaction products under hyperglycemic conditions
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Two novel and two known compounds, 4-quinolylaldoxime and indole-3-aldehyde, were isolated from a reaction mixture consisting of D-glucose and L-tryptophan at physiological temperature and pH. The chemical structures of the two novel compounds were elucidated by spectroscopic analysis such as X-ray crystallography. One of the novel compound and the indole-3-aldehyde showed mutagenicity toward Salmonella typhimurium YG1024 with S9 mix. Furthermore, 4-quinolylaldoxime was detected from streptozotocin-induced diabetic rat plasma by LC-MS/MS analysis; however, the isolated compounds were not detected in rat diet extracts. To our knowledge, this is the first report in which 4-quinolylaldoxime was detected in rat plasma. These results suggest that amino-carbonyl reaction products may be formed in diabetic condition and induce genetic damage.
- Imahori, Daisuke,Matsumoto, Takahiro,Kojima, Naoto,Hasei, Tomohiro,Sumii, Megumi,Sumida, Taishi,Yamashita, Masayuki,Watanabe, Tetsushi
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p. 363 - 367
(2018/04/09)
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- Method for synthesizing indole -3 - formaldehyde compounds (by machine translation)
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The invention relates to a synthetic indole - 3 - formaldehyde compounds, which belongs to the technical field of organic synthesis. The invention will be indole compound, hexamethylene tetramine, crystalline aluminum trichloride, N, N - dimethyl formamide in proportion in 120 °C reaction under the condition of 1 - 20 the H, then filtered, washing, filtering, concentrating, column chromatography purification and other after-treatment technology, make the refined indole - 3 - formaldehyde compound. The invention overcomes the indole - 3 - benzaldehyde compound of preparation need to use not stabilized peroxide, and for a long time under the high temperature reaction of the defect. And the invention uses the advantages of simple equipment, product yield is high, the resulting yield of a target product can be up to 94%. In addition, the invention relates to a low reaction conditions, less catalyst levels, low energy consumption, the post treatment process is simple and easy to use, without the need of using a high dosage of acid or alkali, post-processing the solvent can be recovered and recycled, industrial "three wastes" is discharged little, suitable for large-scale production. (by machine translation)
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Paragraph 0041-0044
(2018/08/28)
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