{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:56:07Z","timestamp":1782129367078,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The natural stilbenoid dehydro-\u03b4-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-\u03b4-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5\u2032-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 \u00b5g\/mL).<\/jats:p>","DOI":"10.3390\/molecules26247594","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T09:02:19Z","timestamp":1639558939000},"page":"7594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis and Antimicrobial Activity of \u03b4-Viniferin Analogues and Isosteres"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0955-3982","authenticated-orcid":false,"given":"Luce Micaela","family":"Mattio","sequence":"first","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Pinna","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1887-1272","authenticated-orcid":false,"given":"Giorgia","family":"Catinella","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-7753","authenticated-orcid":false,"given":"Loana","family":"Musso","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasandra Juliet","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Medical Biology, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Angeliki","family":"Krogfelt","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Medical Biology, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-8922","authenticated-orcid":false,"given":"Sabrina","family":"Dallavalle","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-3348","authenticated-orcid":false,"given":"Andrea","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8976","DOI":"10.1021\/cr500689b","article-title":"Chemistry and Biology of Resveratrol-Derived Natural Products","volume":"115","author":"Keylor","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mattio, L.M., Catinella, G., Dallavalle, S., and Pinto, A. (2020). Stilbenoids: A natural arsenal against Bacterial pathogens. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060336"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pecyna, P., Wargula, J., Murias, M., and Kucinska, M. (2020). More than resveratrol: New insights into stilbene-based compounds. Biomolecules, 10.","DOI":"10.3390\/biom10081111"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3945\/an.115.011627","article-title":"Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy?","volume":"7","author":"Weiskirchen","year":"2016","journal-title":"Adv. Nutr. An Int. Rev. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/ejoc.201501486","article-title":"Total synthesis of the resveratrol oligomers (\u00b1)-Ampelopsin B and (\u00b1)-\u03c3-Viniferin","volume":"2016","author":"Lindgren","year":"2016","journal-title":"Eur. J. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1002\/adsc.201601089","article-title":"Total Synthesis of Viniferifuran, Resveratrol-Piceatannol Hybrid, Anigopreissin A and Analogues\u2014Investigation of Demethylation Strategies","volume":"358","author":"Vo","year":"2016","journal-title":"Adv. Synth. Catal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1021\/ja806183r","article-title":"Total synthesis of diverse carbogenic complexity within the resveratrol class from a common building block","volume":"131","author":"Snyder","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1021\/jacs.0c01714","article-title":"Synthesis of Vitisins A and D Enabled by a Persistent Radical Equilibrium","volume":"142","author":"Romero","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.aaj1597","article-title":"Synthesis of resveratrol tetramers via a stereoconvergent radical equilibrium","volume":"354","author":"Keylor","year":"2016","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6650","DOI":"10.1021\/acs.orglett.8b02638","article-title":"Synthesis of Indole-, Benzo[b]thiophene-, and Benzo[b]selenophene-Based Analogues of the Resveratrol Dimers Viniferifuran and (\u00b1)-Dehydroampelopsin B","volume":"20","author":"Krzyzanowski","year":"2018","journal-title":"Org. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.ejmech.2017.11.099","article-title":"Natural product inspired library synthesis\u2014Identification of 2,3-diarylbenzofuran and 2,3-dihydrobenzofuran based inhibitors of Chlamydia trachomatis","volume":"143","author":"Saleeb","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.3390\/molecules15095909","article-title":"Modular synthesis of polyphenolic benzofurans, and application in the total synthesis of malibatol A and shoreaphenol","volume":"15","author":"Chen","year":"2010","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8927","DOI":"10.1039\/C6OB01657J","article-title":"Total synthesis of diptoindonesin G and its analogues as selective modulators of estrogen receptors","volume":"14","author":"Liu","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1002\/slct.201701490","article-title":"Synthesis of 4-Formyl-2-arylbenzofuran Derivatives by PdCl(C3H5)dppb-Catalyzed Tandem Sonogashira Coupling-Cyclization under Microwave Irradiation\u2014Application to the Synthesis of Viniferifuran Analogues","volume":"2","author":"Vo","year":"2017","journal-title":"ChemistrySelect"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ejmech.2014.11.039","article-title":"Shamsuzzaman Bioactive Benzofuran derivatives: A review","volume":"97","author":"Khanam","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ejmech.2014.11.047","article-title":"Bioactive benzofuran derivatives: Moracins A-Z in medicinal chemistry","volume":"90","author":"Naik","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.pharep.2016.11.007","article-title":"A review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives","volume":"69","author":"Chand","year":"2017","journal-title":"Pharmacol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27510","DOI":"10.1039\/C9RA04917G","article-title":"Natural source, bioactivity and synthesis of benzofuran derivatives","volume":"9","author":"Miao","year":"2019","journal-title":"RSC Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"96809","DOI":"10.1039\/C5RA20658H","article-title":"Benzofuran: An emerging scaffold for antimicrobial agents","volume":"5","author":"Hiremathad","year":"2015","journal-title":"RSC Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7324\/JAPS.2020.102006","article-title":"Antimicrobial evaluation and molecular properties prediction of pyrazolines incorporating benzofuran and pyrazole moieties","volume":"10","author":"Elsherif","year":"2020","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-55975-1","article-title":"Antimicrobial activity of resveratrol-derived monomers and dimers against foodborne pathogens","volume":"9","author":"Mattio","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Catinella, G., Mattio, L.M., Musso, L., Arioli, S., Mora, D., Beretta, G.L., Za, N., Pinto, A., and Dallavalle, S. (2020). Structural Requirements of Benzofuran Derivatives Dehydro-\u03b4-and Dehydro-\u03b5-Viniferin for Antimicrobial Activity Against the Foodborne Pathogen Listeria monocytogenes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062168"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13664","DOI":"10.1021\/acs.joc.0c01835","article-title":"Sequential One-Pot Synthesis of 3-Arylbenzofurans from N-Tosylhydrazones and Bromophenol Derivatives","volume":"85","author":"Lamaa","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1039\/D0OB01115K","article-title":"Synthesis of indenofurans, benzofurans and spiro-lactones: Via Hauser-Kraus annulation involving 1,6-addition of phthalide to quinone methides","volume":"18","author":"Basu","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127260","DOI":"10.1016\/j.molstruc.2019.127260","article-title":"Condensation of ninhydrin with phenols: Regioselective formation of diverse organic scaffolds and crystal structure studies","volume":"1202","author":"Das","year":"2020","journal-title":"J. Mol. Struct."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1021\/acs.joc.8b01358","article-title":"A One-Pot Approach to 2,3-Diarylbenzo[b]furans through N-Heterocyclic Carbene-Catalyzed 1,6-Conjugate Addition Followed by Acid Mediated Dehydrative Annulation","volume":"83","author":"Singh","year":"2018","journal-title":"J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1016\/j.bmc.2019.04.028","article-title":"Discovery of 4,6-bis(benzyloxy)-3-phenylbenzofuran as a novel Pin1 inhibitor to suppress hepatocellular carcinoma via upregulating microRNA biogenesis","volume":"27","author":"Fan","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.1021\/acs.orglett.9b03001","article-title":"Synthesis of Functionalized Benzofurans from para-Quinone Methides via Phospha-1,6-Addition\/ O-Acylation\/Wittig Pathway","volume":"21","author":"Liou","year":"2019","journal-title":"Org. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9280","DOI":"10.1021\/jo961051a","article-title":"Palladium-catalyzed reaction of o-ethynylphenols, o-((trimethylsilyl)ethynyl)phenyl acetates, and o-alkynylphenols with unsaturated triflates or halides: A route to 2-substituted-, 2,3-disubstituted-, and 2-substituted-3-acylbenzo[b]furans","volume":"61","author":"Arcadi","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1016\/j.tet.2013.02.003","article-title":"Efficient microwave-assisted one-pot three-component synthesis of 2,3-disubstituted benzofurans under Sonogashira conditions","volume":"69","author":"Markina","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6022","DOI":"10.1016\/j.bmc.2013.07.037","article-title":"Design, synthesis, biological and structural evaluation of functionalized resveratrol analogues as inhibitors of quinone reductase 2","volume":"21","author":"Jensen","year":"2013","journal-title":"Bioorganic Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1016\/j.bmc.2017.06.035","article-title":"Selective opioid growth factor receptor antagonists based on a stilbene isostere","volume":"25","author":"Stockdale","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1016\/j.bmc.2017.08.016","article-title":"Synthesis of amide isosteres of schweinfurthin-based stilbenes","volume":"25","author":"Stockdale","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/S0040-4020(03)00050-4","article-title":"Stereoselective cyclization of stilbene derived carbocations","volume":"59","author":"Li","year":"2003","journal-title":"Tetrahedron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2174\/138527212799859390","article-title":"Strategies and methods for the syntheses of natural oligomeric stilbenoids and analogues","volume":"16","author":"Velu","year":"2012","journal-title":"Curr. Org. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8680","DOI":"10.1021\/jo401398n","article-title":"2,2\u2032-Biphenols Via Protecting Group-Free Thermal or Microwave-Accelerated Suzuki-Miyaura Coupling in Water","volume":"78","author":"Schmidt","year":"2013","journal-title":"J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/1521-3765(20020118)8:2<408::AID-CHEM408>3.0.CO;2-L","article-title":"End-cap stabilized oligoynes: Model compounds for the linear sp carbon allotrope carbyne","volume":"8","author":"Gibtner","year":"2002","journal-title":"Chem. A Eur. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/cssc.201700101","article-title":"Lignin-Derived Thioacidolysis Dimers: Reevaluation, New Products, Authentication, and Quantification","volume":"10","author":"Yue","year":"2017","journal-title":"ChemSusChem"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1080\/10286020.2020.1776267","article-title":"Total synthesis of the active resveratrol dimer dehydro- \u03b4-viniferin","volume":"22","author":"Teng","year":"2020","journal-title":"J. Asian. Nat. Prod. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1021\/jm100274c","article-title":"Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites","volume":"53","author":"Hoshino","year":"2010","journal-title":"J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/24\/7594\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:48:26Z","timestamp":1760168906000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/24\/7594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,15]]},"references-count":41,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["molecules26247594"],"URL":"https:\/\/doi.org\/10.3390\/molecules26247594","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,15]]}}}