- Macrocyclization of bis-indole quinolines for selective stabilization of G-quadruplex DNA structures
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The recognition of G-quadruplex (G4) DNA structures as important regulatory elements in biological mechanisms, and the connection between G4s and the evolvement of different diseases, has sparked interest in developing small organic molecules targeting G4s. However, such compounds often lack drug-like properties and selectivity. Here, we describe the design and synthesis of a novel class of macrocyclic bis-indole quinolines based on their non-macrocyclic lead compounds. The effects of the macrocyclization on the ability to interact with G4 DNA structures were investigated using biophysical assays and molecular dynamic simulations. Overall, this revealed compounds with potent abilities to interact with and stabilize G4 structures and a clear selectivity for both G4 DNA over dsDNA and for parallel/hybrid G4 topologies, which could be attributed to the macrocyclic structure. Moreover, we obtained knowledge about the structure-activity relationship of importance for the macrocyclic design and how structural modifications could be made to construct improved macrocyclic compounds. Thus, the macrocyclization of G4 ligands can serve as a basis for the optimization of research tools to study G4 biology and potential therapeutics targeting G4-related diseases.
- Andréasson, M?ns,Chorell, Erik,Das, Rabindra Nath,Kumar, Rajendra
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Read Online
- Copper and copper-manganese 1D coordination polymers: Synthesis optimization, crystal structure and preliminary studies as catalysts for Baylis–Hillman reactions
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This work reports the influence of experimental parameters (pH and counter-ion) in the synthesis of the 1D coordination polymer [Cu(IDA)(H2O)2]n (IDA = iminodiacetate), named here Cu-IDA. Copper-manganese bimetallic coordi
- Alves Júnior, Severino,Chojnacki, Jaroslaw,Lima-Junior, Claudio Gabriel,Silva, Lucas Araujo Trajano,Vasconcellos, Mário Luiz Araújo de Almeida,da Silva, Fausthon Fred,da Silva, R. B.,de Andrade, Julyanna Candido Dutra
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Read Online
- Accelerating the optimization of enzyme-catalyzed synthesis conditionsviamachine learning and reactivity descriptors
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Enzyme-catalyzed synthesis reactions are of crucial importance for a wide range of applications. An accurate and rapid selection of optimal synthesis conditions is crucial and challenging for both human knowledge and computer predictions. In this work, a
- Liang, Jinhu,Liu, Dongchang,Wan, Zhongyu,Wang, Quan-De
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supporting information
p. 6267 - 6273
(2021/07/28)
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- Phosphine-Catalyzed [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates with Isoxazole-Based Alkenes
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A phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford various multifunctional isoxazoles in moderate to good yields with moderate to excellent diastereoselectivities. With a spirocyclic chiral phosphine as the catalyst, up to 89% ee was obtained.
- Liao, Jianning,Dong, Jipan,Xu, Jiaqing,Wang, Wei,Wu, Yongjun,Hou, Yuxia,Guo, Hongchao
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supporting information
p. 2090 - 2099
(2021/02/05)
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- New allyldithiocarbimate salts: Synthesis, structure and antifungal activity
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Fifteen new allyldithiocarbimates were prepared from different allylic bromides and various potassium dithiocarbimates, yielding (Z)-2-(methoxycarbonyl)-3-(X-nitrophenyl)allyl-(N-R-sulfonyl)dithiocarbimates (where X = 2, 3 and 4; R = phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl and 4-iodophenyl). These anions were isolated as tetraphenylphosphonium salts and characterized by HRMS, infrared, 1H and 13C NMR spectroscopies. Molecular electrostatic potentials were used to evaluate intermolecular interactions present in the new substances and to explain variations observed on their melting points. Single crystal X-ray diffraction experiments confirmed the Z stereochemistry of the allyldithiocarbimate anions. C–H?O, C–H?N, C–H?S and C–H?π intermolecular interactions in the solid state were studied by X-ray diffraction and Hirshfeld surface analyses. The new compounds inhibited the mycelial growth of various fungi species responsible for severe plant diseases. The allylithiocarbimates were especially active against Botrytis cinerea, with IC50 values as low as 20 μM, being more effective than the active principals of the commercial fungicides Ziram and Mancozeb.
- Albuini-Oliveira, Nathália M.,Alvarez, Natalia,Ellena, Javier,Guilardi, Silvana,Lima, Marcelo S.,Rubinger, Mayura M. M.,Souza, Rafael A. C.,Tavares, Eder C.,Vidigal, Antonio E. C.,Zacchi, Carlos H. C.,Zambolim, Laercio
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- Enantioselective Lewis base catalyzed phosphonyldifluoromethylation of allylic fluorides using a: C -silyl latent pronucleophile
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The first enantioselective phosphonyldifluoromethylation is enabled by the use of diethyl (difluoro(trimethylsilyl)-methyl)phosphonate reagent as a latent pronucleophile in the Lewis base catalyzed substitution of allylic fluorides. The reaction proceeds
- Zi, You,Lange, Markus,Vilotijevic, Ivan
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supporting information
p. 5689 - 5692
(2020/06/19)
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- α-ZrP/Uracil/Cu2+ nanoparticles as an efficient catalyst in the Morita-Baylis-Hillman reaction
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A facile synthesis of uracil-Cu2+ nanoparticles immobilized on alpha-zirconium hydrogen phosphate (α-ZrP), abbreviated as α-ZrP/Uracil/Cu2+, was presented. This compound was synthesized by the thermal method and used as a reusable ca
- Hajipour, Abdol R.,Zakery, Saedeh
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- Effective and diastereoselective preparation of dispiro[cyclopent-3′-ene]bisoxindoles: Via novel [3 + 2] annulation of isoindigos and MBH carbonates
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A novel and diastereoselective [3 + 2] annulation of isoindigos and Morita-Baylis-Hillman carbonates has been developed for the highly efficient and one-step preparation of highly steric dispiro[cyclopent-3′-ene]bisoxindoles with two all-carbon quaternary
- Ren, Hong-Xia,Peng, Lin,Song, Xiang-Jia,Liao, Li-Guo,Zou, Ying,Tian, Fang,Wang, Li-Xin
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supporting information
p. 1297 - 1304
(2018/03/06)
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- On the tandem Morita-Baylis-Hillman/transesterification processes. Mechanistic insights for the role of protic solvents
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Despite the remarkable rate acceleration under protic solvents such as alcohols and water, the use of acrylates as activated alkenes places a problem due to the possibility of ester hydrolysis or transesterification. Therefore, the tandem transesterification/Morita-Baylis-Hillman (MBH) reactions were investigated by ESI(+)-MS/(MS) and 1H NMR techniques. For the first time, the MBH back-reaction was fully examined by ESI(+)-MS/(MS) using labelling reagents revealed the complex equilibrium involving the Michael-type addition step of DABCO to acrylate. C- and O-protonation were observed at this stage, showing the transesterification process occurs previous to the aldol step, which is the rate-determining step of the mechanism. At this stage, a short-lived tetrahedral intermediate might be involved and should be considered in these processes.
- Carpanez, Arthur G.,Coelho, Fernando,Amarante, Giovanni W.
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- Synthesis and in vitro anti Leishmania amazonensis biological screening of Morita-Baylis-Hillman adducts prepared from eugenol, thymol and carvacrol
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Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC50 values in the range of 22.30-4.71 μM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism.
- Seixas Xavier, Francisco José,Da Franca Rodrigues, Klinger Antonio,De Oliveira, Ramon Guerra,Lima, Claudio Gabriel,Da Camara Rocha, Juliana,Keesen, Tatjana Souza Lima,De Oliveira, Marcia Rosa,Silva, Fábio Pedrosa Lins,De Almeida Vasconcellos, Mário Luiz Araújo
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- Star-like polyionic heterogeneous nanocatalyst as a highly active catalyst for promotion of Baylis-Hillman reaction in [bmim]Cl
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The use of star-like polyionic Lewis base heterogeneous nanocatalyst for the Baylis-Hillman reaction of benzyl- and methylacrylates with aryl aldehydes has been investigated. The corresponding Baylis-Hillman adducts are obtained in good to high yields in
- Valizadeh, Hassan,Shomali, Ashkan,Noorshargh, Saeideh
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p. 2169 - 2177
(2015/10/19)
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- N-bromosuccinimide-mediated radical cyclization of 3-arylallyl azides: Synthesis of 3-substituted quinolines
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Visible light irradiation of N-bromosuccinimide serves as an effective means to convert methyl 2-(azidomethyl)-3-arylpropenoates and 2-(azidomethyl)-3-arylacrylonitriles to the corresponding iminyl radicals via ?±-hydrogen abstraction and subsequent extrusion of dinitrogen. Thus formed iminyl radicals then undergo intramolecular ortho attack on the aryl ring, affording methyl quin-oline-3-carboxylates and quinoline-3-carbonitriles respectively.
- Wang, Wei-Xia,Zhang, Qing-Zhao,Zhang, Tian-Qi,Li, Zhan-Shan,Zhang, Wei,Yu, Wei
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supporting information
p. 221 - 226
(2015/02/19)
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- Synthesis, characterization and antimicrobial activity of some new Baylis-Hillman derived benzothiazolo pyrimidinone derivatives
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A series of Baylis-Hillman derived 22 new benzothiazolo pyrimidinone derivatives have been synthesized from Baylis-Hillman acetates and 2-amino benzothiazole under neat conditions with high yields. All the newly synthesized compounds have been characteriz
- Gampa, Raghavachary,Chebrolu, Lavanya Devi,Jarapula, Ravi,Vaidya, Jayathirtha Rao,Ghanakota, Venkateshwar Rao,Manda, Sarangapani
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p. 217 - 227
(2015/03/04)
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- Electrochemical and computational studies, in protic medium, of Morita-Baylis-Hillman adducts and correlation with leishmanicidal activity
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Enzymatic bioreduction of nitro groups plays an important role on the activity of biologically active nitroaromatic compounds. Electrochemical methods are useful tools to simulate in vivo metabolic processes. This work presents electrochemical studies, in
- De Paiva, Yen G.,Pinho Júnior, Waldomiro,De Souza, Antonio A.,Costa, Cícero O.,Silva, Fábio P.L.,Lima-Junior, Cláudio G.,Vasconcellos, Mario L.A.A.,Goulart, Marília O.F.
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p. 557 - 563
(2015/02/02)
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- A multi-component reaction in the Morita-Baylis-Hillman route
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A facile stereoselective synthesis of trisubstituted (Z)/(E)-alkenes containing a functionalized thioether unit has been accomplished by using a new three-component tetramolecular reaction (ABCB′-type) following a Morita-Baylis-Hillman (MBH) route. Synthe
- Pal, Sudhir Chandra,Bhunia, Sankar Chandra
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p. 4816 - 4822
(2013/08/23)
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- An efficient and recyclable DMAP-based ionic liquid/water system for Morita-Baylis-Hillman reactions
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The efficient and recyclable system, DMAP-based ionic liquid/water, has been developed and used in the Morita-Baylis-Hillman reaction of aromatic aldehydes with acrylates. The coupling reactions under the described basic reaction conditions proceed quickl
- Zhang, Li-Rong,Yi, Feng-Ping,Zhang, Xuan,Zou, Jian-Zhong
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experimental part
p. 418 - 420
(2012/09/22)
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- Correlation between electrochemical and theoretical studies on the leishmanicidal activity of twelve Morita-Baylis-Hillman adducts
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Enzymatic bioreduction of nitro groups plays an important role on the activity of biologically active nitroaromatic compounds. Electrochemical methods are useful tools to simulate in vivo metabolic processes. This work presents electrochemical studies in
- De Paiva, Yen G.,De Souza, Anto?nio A.,Lima-Junior, Claudio G.,Silva, Fa?bio P. L.,Filho, Edilson B. A.,De Vasconcelos, Camila C.,De Abreu, Fabiane C.,Goulart, Mari?lia O. F.,Vasconcellos, Ma?rio L. A. A.
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scheme or table
p. 894 - 904
(2012/06/18)
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- Microwave-assisted synthesis of the (E)-α-methylalkenoate framework from multifunctionalized allylic phosphonium salts
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A convenient and general microwave-assisted method for the synthesis of stereochemically defined α-methylalkenoic acids and esters from allylic phosphonium salts in a basic aqueous medium is described. A selective preparation of acids or esters was dependent on the base (NaOH or NaHCO 3) employed in the reaction and could be achieved with good to excellent yields under mild conditions in the absence of hydrides and reducing agents.
- Meier, Lidiane,Ferreira, Misael,Sa, Marcus M.
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body text
p. 179 - 186
(2012/07/14)
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- Microwave irradiation or low temperature improved synthesis of antiparasitic morita-baylis-hillman adducts
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It is reported the synthesis of 24 Morita-Baylis-Hillman adducts (3a-3l/6a-6l) using microwave irradiation at 80 °C or conventional protocol at 0 °C to promote the reactions between aromatic aldehydes and methyl acrylate or acrylonitrile (81-99%). It is shown that the reaction of 2-hydroxy(4-bromophenyl)methyl acrylate formation is reversible at 120 °C.
- Claudio Jr.,Silva, Fabio P.L.,De Oliveira, Ramon G.,Subrinho, Fernanda L.,De Andrade, Natalia G.,Vasconcellos, Mario L.A.A.
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scheme or table
p. 2220 - 2224
(2012/02/03)
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- Fluorous tagging of DABCO through halogen bonding: Recyclable catalyst for the Morita-Baylis-Hillman reaction
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The halogen-bonded adduct between DABCO and two molecules of perfluorooctyl iodide (DABCO·(C8F17I)2) acts as a recyclable organocatalyst for the Morita-Baylis-Hillman reaction. This "supramolecular fluorous catalyst" is re
- Dordonne, Sophie,Crousse, Benoit,Bonnet-Delpon, Daniele,Legros, Julien
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supporting information; experimental part
p. 5855 - 5857
(2011/06/28)
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- Synthesis of allyl aryl sulfone derivatives from Baylis-Hillman acetates in water
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Various phenyl and p-tolyl allyl sulfone derivatives were prepared stereoselectively by reacting Baylis-Hillman acetates with sodium 4-R-benzenesulfinate (R=H, Me) in H2O. The reaction was very efficient in providing the corresponding sulfone d
- Karnakar, Konkala,Shankar, Jilla,Murthy, Sabbavarapu Narayana,Nageswar, Yadavalli Venkata Durga
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body text
p. 875 - 880
(2011/06/27)
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- Lewis base catalyzed enantioselective allylic hydroxylation of Morita-Baylis-Hillman carbonates with water
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A Lewis base catalyzed allylic hydroxylation of Morita-Baylis-Hillman (MBH) carbonates has been developed. Various chiral MBH alcohols can be synthesized in high yields (up to 99%) and excellent enantioselectivities (up to 94% ee). This is the first report using water as a nucleophile in asymmetric organocatalysis. The nucleophilic role of water has been verified using 18O-labeling experiments.
- Zhu, Bo,Yan, Lin,Pan, Yuanhang,Lee, Richmond,Liu, Hongjun,Han, Zhiqiang,Huang, Kuo-Wei,Tan, Choon-Hong,Jiang, Zhiyong
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experimental part
p. 6894 - 6900
(2011/10/09)
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- Efficient synthesis of 16 aromatic Morita-Baylis-Hillman adducts: Biological evaluation on Leishmania amazonensis and Leishmania chagasi
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Sixteen aromatic Morita-Baylis-Hillman adducts (MBHA) 1-16 were efficiently synthesized in a one step Morita-Baylis-Hillman reaction (MBHR) involving commercial aldehydes with methyl acrylate or acrylonitrile (81-100% yields) without the formation of side
- Junior, Claudio G.L.,De Assis, Priscila A.C.,Silva, Fabio P.L.,Sousa, Suervy C.O.,De Andrade, Natalia G.,Barbosa, Ticiano P.,Neris, Patricia L.N.,Segundo, Luiz V.G.,Anjos, Italo C.,Carvalho, Gabriel A.U.,Rocha, Gerd B.,Oliveira, Marcia R.,Vasconcellos, Mario L.A.A.
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experimental part
p. 279 - 284
(2011/02/22)
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- The first one-pot synthesis of Morita-Baylis-Hillman adducts starting directly from alcohols
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The first example of one-pot oxidative carbon-carbon bond formation via the Morita-Baylis-Hillman reaction using alcohols is reported. The protocol involves silica gel-DABCO catalyzed oxidation of alcohols to aldehydes with chloramine-T followed by their
- Yadav, Lal Dhar Singh,Srivastava, Vishnu Prabhakar,Patel, Rajesh
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experimental part
p. 1047 - 1050
(2010/06/13)
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- Magnetic nanoparticle-supported Morita-Baylis-Hillman catalysts
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A magnetic nanoparticle-supported quinuclidine was prepared and evaluated as a recoverable Morita-Baylis-Hillman catalyst. The supported catalyst 2 demonstrated comparable activity with that of DABCO and could be simply recycled with the assistance of an
- Luo, Sanzhong,Zheng, Xiaoxi,Xu, Hui,Mi, Xueling,Zhang, Long,Cheng, Jin-Pei
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p. 2431 - 2434
(2008/09/19)
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- Hydroxyl ionic liquid (HIL)-immobilized quinuclidine for Baylis-Hillman catalysis: Synergistic effect of ionic liquids as organocatalyst supports
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Hydroxyl ionic liquid (HIL) has been explored as a novel support for Baylis-Hillman catalyst. The HIL-supported catalyst showed a better catalytic activity compared to other IL-immobilized catalyst that has no hydroxyl group attached to the IL scaffold. T
- Mi, Xueling,Luo, Sanzhong,Xu, Hui,Zhang, Long,Cheng, Jin-Pei
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p. 2537 - 2544
(2007/10/03)
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- Study of the Baylis-Hillman reaction in a microreactor environment: First continuous production of Baylis-Hillman Adducts
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The Baylis-Hillman reaction has been optimized for use under microreactor conditions. After optimization, the reaction could be performed continuously and approximately 30% faster compared to batch conditions, however at a quite low flow rate.
- Acke, Davy R. J.,Stevens, Christian V.
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p. 417 - 422
(2012/12/22)
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- Ionic liquid-immobilized quinuclidine-catalyzed Morita-Baylis-Hillman reactions
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(Chemical Equation Presented) The ionic liquid-bound quinuclidine catalyzed Baylis-Hillman reactions were investigated. The IL-supported catalyst showed equally good catalytic activity as compared with its nonimmobilized counterpart. The corresponding Bay
- Mi, Xueling,Luo, Sanzhong,Cheng, Jin-Pei
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p. 2338 - 2341
(2007/10/03)
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- N-methylpiperidine - A useful base catalyst in the Morita-Baylis-Hillman reaction
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N-methylpiperidine, a commercially available mild base, has effectively been utilized as a catalyst in the Morita-Baylis-Hillman reaction. Moderate to excellent yields (34-95%) and significant rate enhancement have been observed. Copyright Taylor & Franci
- Zhao, San-Hu,Chen, Zhao-Bin
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p. 3045 - 3053
(2007/10/03)
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- Reexamination of the traditional Baylis-Hillman reaction
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In the Baylis-Hillman reaction of arylaldehydes with methyl vinyl ketone (MVK), we found that, besides the normal Baylis-Hillman adduct 1, the diadduct 2 can also be formed at the same time and the yield of 2 can reach to 55% if increasing the amount of methyl vinyl ketone. But for ethyl vinyl ketone (EVK), methyl acrylate or acrylonitrile, only the normal Baylis-Hillman adduct 4, 7 or 8 was obtained, respectively. The substituent's effects and Lewis base effects were also examined and a plausible reaction mechanism was proposed for the formation of 2.
- Shi, Min,Li, Chao-Qun,Jiang, Jian-Kang
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p. 1181 - 1189
(2007/10/03)
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- The Baylis-Hillman chemistry in aqueous media: Elucidation of mechanism for synthesis of ether side-product leads to an efficient approach to C-O bond formation
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The formation of an ether from the Baylis-Hillman (BH) adduct during the BH reaction of 5-isoxazolecarboxaldehydes is a common phenomenon if the reaction is allowed to proceed for longer periods. The amount of formation of such ethers depends on the acryl
- Patra,Roy,Joshi,Roy,Batra,Bhaduri
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p. 663 - 670
(2007/10/03)
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- The Baylis-Hillman reaction under high pressure induced by water-freezing
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High pressure (about 200 MPa), which was realized by freezing water in a sealed autoclave, has been successfully applied to the Baylis-Hillman reaction, in which an efficient rate enhancement was observed.
- Hayashi, Yujiro,Okado, Kotaro,Ashimine, Itaru,Shoji, Mitsuru
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p. 8683 - 8686
(2007/10/03)
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- Efficient Baylis-Hillman reaction using stoichiometric base catalyst and an aqueous medium
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A practical and efficient set of conditions were developed using stoichiometric base catalyst, 1,4-diazabicyclo[2,2,2]octane (DABCO), and an aqueous medium to overcome problems commonly associated with the Baylis-Hillman reaction, such as low reaction yields and long reaction time. These simple modifications to the classical conditions, using more base catalyst and an aqueous medium, proved to be successful in converting a variety of aliphatic and aromatic aldehydes to their corresponding Baylis-Hillman products. The inclusion of environmentally friendly water in the reaction solvent was critical for achieving the high yield of Baylis-Hillman adducts. Our deuterium-exchange experiments suggest that the Michael addition adduct formed between DABCO and methyl acrylate is the active intermediate for the Baylis-Hillman reaction in aqueous conditions, and its hydrolysis, a nonproductive side reaction facilitated by the quaternary ammonium ion, leading to the formation of a stable betaine product, consumes both the catalyst and methyl acrylate, making it necessary to add more base catalyst and methyl acrylate.
- Yu,Liu,Hu
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p. 5413 - 5418
(2007/10/03)
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