ACS Publications. Most Trusted. Most Cited. Most Read
Synthesis of a 3-(α-Styryl)benzo[b]-thiophene Library via Bromocyclization of Alkynes and Palladium-Catalyzed Tosylhydrazones Cross-Couplings: Evaluation as Antitubulin Agents

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Comb. Sci. 2014, 16, 12, 702-710
    Research Article

    Synthesis of a 3-(α-Styryl)benzo[b]-thiophene Library via Bromocyclization of Alkynes and Palladium-Catalyzed Tosylhydrazones Cross-Couplings: Evaluation as Antitubulin Agents
    Click to copy article linkArticle link copied!

    View Author Information
    † Univ Paris Sud, CNRS, BioCIS−UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry, F-92296, France
    ‡ Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, avenue de la Terrasse, F-91198 Gif sur Yvette, France
    *E-mail: [email protected]
    *E-mail: [email protected]
    Other Access OptionsSupporting Information (1)

    ACS Combinatorial Science

    Cite this: ACS Comb. Sci. 2014, 16, 12, 702–710
    Click to copy citationCitation copied!
    https://doi.org/10.1021/co500115b
    Published September 17, 2014
    Copyright © 2014 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    A library of functionalized 3-(α-styryl)-benzo[b]thiophenes, endowed with a high level of molecular diversity, was efficiently synthesized by applying a synthetic sequence that allowed introduction of various substituents on aromatic A, B, and C-rings. The strategy developed involves the synthesis of 3-bromobenzo[b]thiophene derivatives through a bromocyclization step of methylthio-containing alkynes using N-methylpyrrolidin-2-one hydrotribromide reagent (MPHT). Further coupling of 3-bromobenzothiophenes under palladium-catalysis with N-tosylhydrazones efficiently furnished 2-aryl-3-(α-styryl)benzo[b]thiophene derivatives. The antiproliferative properties of target compounds were studied. Among them, compound 5m has demonstrated submicromolar cytotoxic activity against HCT-116 cell line, and inhibited the polymerization of tubulin at micromolar level comparable to that of CA-4.

    Copyright © 2014 American Chemical Society

    Subjects

    what are subjects

    Keywords

    what are keywords

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    Experimental details about synthesis and characterization of compounds, biological and computational methods, copies of 1HNMR, and 13C NMR spectra of all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai
    powered by  Scite

    This article is cited by 27 publications.

    1. Xiaolong Zhang, Paramasivam Sivaguru, Yongzhen Pan, Nan Wang, Wenjie Zhang, Xihe Bi. The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future. Chemical Reviews 2025, 125 (2) , 1049-1190. https://doi.org/10.1021/acs.chemrev.4c00742
    2. Diana Lamaa, Camille Hauguel, Hsin-Ping Lin, Estelle Messe, Vincent Gandon, Mouad Alami, Abdallah Hamze. Sequential One-Pot Synthesis of 3-Arylbenzofurans from N-Tosylhydrazones and Bromophenol Derivatives. The Journal of Organic Chemistry 2020, 85 (21) , 13664-13673. https://doi.org/10.1021/acs.joc.0c01835
    3. Tourin Bzeih, Kena Zhang, Ali Khalaf, Ali Hachem, Mouad Alami, Abdallah Hamze. One-Pot Reaction between N-Tosylhydrazones and 2-Nitrobenzyl Bromide: Route to NH-Free C2-Arylindoles. The Journal of Organic Chemistry 2019, 84 (1) , 228-238. https://doi.org/10.1021/acs.joc.8b02623
    4. Parul Garg and Anand Singh . Unmasking Dipole Character of Acyl Ketene Dithioacetals via a Cascade Reaction with Arynes: Synthesis of Benzo[b]thiophenes. Organic Letters 2018, 20 (5) , 1320-1323. https://doi.org/10.1021/acs.orglett.8b00053
    5. Charlotte Gény, Alma Abou Samra, Pascal Retailleau, Bogdan I. Iorga, Hristo Nedev, Khalijah Awang, Fanny Roussi, Marc Litaudon, and Vincent Dumontet . (+)- and (−)-Ecarlottones, Uncommon Chalconoids from Fissistigma latifolium with Pro-Apoptotic Activity. Journal of Natural Products 2017, 80 (12) , 3179-3185. https://doi.org/10.1021/acs.jnatprod.7b00494
    6. Tourin Bzeih, Diana Lamaa, Gilles Frison, Ali Hachem, Nada Jaber, Jerome Bignon, Pascal Retailleau, Mouad Alami, and Abdallah Hamze . Csp2–Csp2 and Csp2–N Bond Formation in a One-Pot Reaction between N-Tosylhydrazones and Bromonitrobenzenes: An Unexpected Cyclization to Substituted Indole Derivatives. Organic Letters 2017, 19 (24) , 6700-6703. https://doi.org/10.1021/acs.orglett.7b03422
    7. Ying Xia, Di Qiu, and Jianbo Wang . Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion. Chemical Reviews 2017, 117 (23) , 13810-13889. https://doi.org/10.1021/acs.chemrev.7b00382
    8. M. G. Finn (Editor-in-Chief). Technical Advances in Medicinal Chemistry. ACS Combinatorial Science 2017, 19 (5) , 277-278. https://doi.org/10.1021/acscombsci.7b00053
    9. Charlotte Gény, Gwladys Rivière, Jérome Bignon, Nicolas Birlirakis, Eric Guittet, Khaljah Awang, Marc Litaudon, Fanny Roussi, and Vincent Dumontet . Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions. Journal of Natural Products 2016, 79 (4) , 838-844. https://doi.org/10.1021/acs.jnatprod.5b00915
    10. Maxime Roche, Salim Mmadi. Salim, Jérôme Bignon, Hélène Levaique, Jean-Daniel Brion, Mouad Alami, and Abdallah Hamze . Palladium-Catalyzed One-Pot Reaction of Hydrazones, Dihaloarenes, and Organoboron Reagents: Synthesis and Cytotoxic Activity of 1,1-Diarylethylene Derivatives. The Journal of Organic Chemistry 2015, 80 (13) , 6715-6727. https://doi.org/10.1021/acs.joc.5b00880
    11. Yong-Sang Kim, Se Hun Kwak, and Young-Dae Gong . Application of Thio-Ugi Adducts for the Preparation of Benzo[b]thiophene and S-Heterocycle Library via Copper Catalyzed Intramolecular C–S Bond Formation. ACS Combinatorial Science 2015, 17 (6) , 365-373. https://doi.org/10.1021/acscombsci.5b00034
    12. Yinqiao Wang, Jiaxi Xu. Dearomatic Sulfur‐Shifted Ene Reaction of 3‐Thiiranylbenzo[ b ]Thiophenes and Ketenes: Further Studies and Experimental Evidence. Asian Journal of Organic Chemistry 2025, https://doi.org/10.1002/ajoc.202500159
    13. Paramasivam Sivaguru, Yongzhen Pan, Nan Wang, Xihe Bi. Who is Who in the Carbene Chemistry of N ‐Sulfonyl Hydrazones. Chinese Journal of Chemistry 2024, 42 (17) , 2071-2108. https://doi.org/10.1002/cjoc.202300716
    14. Pritam Saha, Koushik Mukherjee. Sonogashira reaction cum cyclization under microwave irradiation supported by sodium aluminate (NaAlO2) and catalyzed by zinc: A green alternative approach in production of furo[3,2-h]quinolones. Materials Today: Proceedings 2023, 80 , 762-768. https://doi.org/10.1016/j.matpr.2022.11.083
    15. Zhi-Chun Zheng, Cun Yang, Xin Kuang, Chang-Hua Ding. Thiophenes and Their Benzo Derivatives: Synthesis. 2022, 519-612. https://doi.org/10.1016/B978-0-12-409547-2.14932-7
    16. Jan Radolko, Peter Ehlers, Peter Langer. Recent Advances in Transition‐Metal‐Catalyzed Reactions of N‐Tosylhydrazones. Advanced Synthesis & Catalysis 2021, 363 (15) , 3616-3654. https://doi.org/10.1002/adsc.202100332
    17. Abdallah Hamze, Mouad Alami, Olivier Provot. Developments of isoCombretastatin A-4 derivatives as highly cytotoxic agents. European Journal of Medicinal Chemistry 2020, 190 , 112110. https://doi.org/10.1016/j.ejmech.2020.112110
    18. Yangjie Fu, Zhaohui Wang, Qiyu Zhang, Zhiyu Li, Hong Liu, Xiaoling Bi, Jiang Wang. Ru( ii )-catalyzed C6-selective C–H acylmethylation of pyridones using sulfoxonium ylides as carbene precursors. RSC Advances 2020, 10 (11) , 6351-6355. https://doi.org/10.1039/C9RA10749E
    19. Neetu Yadav, Vijay B. Yadav, Mohd Danish Ansari, Hozeyfa Sagir, Ankit Verma, I. R. Siddiqui. Catalyst-free synthesis of 2,3-dihydro-1,5-benzothiazepines in a renewable and biodegradable reaction medium. New Journal of Chemistry 2019, 43 (18) , 7011-7014. https://doi.org/10.1039/C8NJ05611K
    20. Oskía Bueno, Gloria Tobajas, Ernesto Quesada, Juan Estévez-Gallego, Sam Noppen, María-José Camarasa, José-Fernando Díaz, Sandra Liekens, Eva-María Priego, María-Jesús Pérez-Pérez. Conformational mimetics of the α-methyl chalcone TUB091 binding tubulin: Design, synthesis and antiproliferative activity. European Journal of Medicinal Chemistry 2018, 148 , 337-348. https://doi.org/10.1016/j.ejmech.2018.02.019
    21. Ahmad Shaabani, Seyyed Emad Hooshmand. Malononitrile dimer as a privileged reactant in design and skeletal diverse synthesis of heterocyclic motifs. Molecular Diversity 2018, 22 (1) , 207-224. https://doi.org/10.1007/s11030-017-9807-y
    22. Di Qiu, Fanyang Mo, Yan Zhang, Jianbo Wang. Recent Advances in Transition-Metal-Catalyzed Cross-Coupling Reactions With N -Tosylhydrazones. 2017, 151-219. https://doi.org/10.1016/bs.adomc.2017.04.002
    23. Ying Xia, Jianbo Wang. N-Tosylhydrazones: versatile synthons in the construction of cyclic compounds. Chemical Society Reviews 2017, 46 (8) , 2306-2362. https://doi.org/10.1039/C6CS00737F
    24. Tanay Kesharwani, Cory T. Kornman, Amanda L. Tonnaer, Andrew D. Royappa. Green synthesis of benzo[b]thiophenes via iron(III) mediated 5-endo-dig iodocyclization of 2-alkynylthioanisoles. Tetrahedron Letters 2016, 57 (3) , 411-414. https://doi.org/10.1016/j.tetlet.2015.12.037
    25. Poojan K. Patel, Jignesh P. Dalvadi, Kishor H. Chikhalia. A direct facile and effective synthesis of various 1,1-heterodiaryl alkenes through Pd catalyzed cross coupling reaction using N-tosylhydrazones via C–OH bond activation. Tetrahedron Letters 2015, 56 (47) , 6585-6589. https://doi.org/10.1016/j.tetlet.2015.10.022
    26. Marie Lawson, Jérôme Bignon, Jean‐Daniel Brion, Abdallah Hamze, Mouad Alami. Transition‐Metal‐Free Synthesis of Polysubstituted Cyclopropane Derivatives from N ‐Tosylhydrazones and their Cytotoxic Activities. Asian Journal of Organic Chemistry 2015, 4 (10) , 1144-1154. https://doi.org/10.1002/ajoc.201500289
    27. N.K. Terrett. Combinatorial Chemistry Online Volume 17, Issue 2, February 2015. Combinatorial Chemistry - an Online Journal 2015, 17 (2) , 5-7. https://doi.org/10.1016/j.comche.2014.12.002
    Download PDF
    Go to ACS Combinatorial Science
    Get e-Alerts
    Get e-Alerts

    ACS Combinatorial Science

    Cite this: ACS Comb. Sci. 2014, 16, 12, 702–710
    Click to copy citationCitation copied!
    https://doi.org/10.1021/co500115b
    Published September 17, 2014
    Copyright © 2014 American Chemical Society
    Request reuse permissions

    Article Views

    1105

    Altmetric

    -

    Citations

    27
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.