{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:20:01Z","timestamp":1788362401247,"version":"build-2803163510"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/na","name":"Inserm Transfert","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Uridine derivatives undergo a diastereospecific intramolecular hetero Michael addition onto uracil C6 to give cyclo-adducts. In contrast to the potent amine and thiol nucleophiles at the 5\u2032 position of ribose, which readily give the N- and S-cyclonucleosides in good yields, the cyclization reaction from the \u201cnatural\u201d 5\u2032-hydroxyl is tedious and has so far been overlooked most probably because of the thermodynamic instability of the O-cyclo-adduct. Here, we show that the O-cyclonucleoside 1 can be isolated, although in low isolated yields, in acidic conditions following an original mechanism. Whether such cyclization reactions occur from biologically relevant pyrimidine-based nucleosides is an open question of interest. Given the structures of thymidine-based antiviral drugs, our results suggest a new hypothetical mode of action for these drugs.<\/jats:p>","DOI":"10.1021\/acsomega.0c03348","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T20:11:06Z","timestamp":1600200666000},"page":"24746-24753","source":"Crossref","is-referenced-by-count":4,"title":["Intramolecular Michael Additions in Uridine Derivatives:\nIsolation of the Labile 5\u2032O-C6 Cyclonucleoside"],"prefix":"10.1021","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0942-9087","authenticated-orcid":true,"given":"Arnaud","family":"Gissot","sequence":"first","affiliation":[{"name":"Univ. Bordeaux , , ,","place":["Bordeaux, France, F-33000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5270-2061","authenticated-orcid":true,"given":"Ste\u0301phane","family":"Massip","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux , , 2 Rue Escarpit , ,","place":["Pessac, France, F-33600"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-0579","authenticated-orcid":true,"given":"Philippe","family":"Barthe\u0301le\u0301my","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux , , ,","place":["Bordeaux, France, F-33000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2026090210483687500_cit1","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1021\/cr900329y","article-title":"Preparation\nof Cyclonucleosides","volume":"110","author":"Mieczkowski","year":"2010","journal-title":"Chem. Rev."},{"key":"2026090210483687500_cit2","doi-asserted-by":"publisher","first-page":"8517","DOI":"10.1016\/S0040-4039(00)78425-5","article-title":"An Improved Synthesis of 2\u2032-Azido-2\u2032-Deoxyuridine","volume":"35","author":"Kirschenheuter","year":"1994","journal-title":"Tetrahedron Lett."},{"key":"2026090210483687500_cit3","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1021\/jo701727h","article-title":"Efficient\nSynthesis of [2\u2018-18O]Uridine and Its Incorporation into Oligonucleotides:\nA New Tool for Mechanistic Study of Nucleotidyl Transfer Reactions\nby Isotope Effect Analysis","volume":"73","author":"Dai","year":"2008","journal-title":"J. Org. Chem."},{"key":"2026090210483687500_cit4","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1021\/np0502692","article-title":"N3,5\u2018-Cycloxanthosine, the First Natural Occurrence\nof a Cyclonucleoside","volume":"68","author":"Capon","year":"2005","journal-title":"J. Nat. Prod."},{"key":"2026090210483687500_cit5","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.3390\/md10112509","article-title":"Further Investigation\nof the Mediterranean Sponge Axinella Polypoides: Isolation of a New\nCyclonucleoside and a New Betaine","volume":"10","author":"Menna","year":"2012","journal-title":"Mar. Drugs"},{"key":"2026090210483687500_cit6","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1039\/c0cs00061b","article-title":"Purine 5\u2032,8-Cyclonucleoside\nLesions: Chemistry and Biology","volume":"40","author":"Chatgilialoglu","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"2026090210483687500_cit7","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the\nPast 50 Years","volume":"29","author":"De Clercq","year":"2016","journal-title":"Clin Microbiol Rev"},{"key":"2026090210483687500_cit8","unstructured":"Harnden, M. R.; Mock, G. A.\n          Antiviral Agents,\nTheir Preparation and Use. EP0060099A1, September\n15, 1982."},{"key":"2026090210483687500_cit9","unstructured":"Chun, B.-K.; Hassan, A.; Hollecker, L.; Stuyver, L. J.; Wang, P.; Watanabe, K. A.\n          Compounds with\nthe bicyclo[4.2.1]nonane system for the treatment of flaviviridae\ninfections. WO2004013300A2, February 12, 2004."},{"key":"2026090210483687500_cit10","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.2174\/092986710790979962","article-title":"Potential\nand Perspectives of Cyclonucleosides","volume":"17","author":"Mieczkowski","year":"2010","journal-title":"Curr.\nMed. Chem."},{"key":"2026090210483687500_cit11","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1021\/jm00227a016","article-title":"Reactions\nof 2-Acyloxyisobutyryl Halides with Nucleosides. 6. Synthesis and\nBiological Evaluation of Some 3\u2019-Acyl Derivatives of 2,2\u2032-Anhydro-1-(.Beta.-D-Arabinofuranosyl)Cytosine\nHydrochloride","volume":"19","author":"Hamamura","year":"1976","journal-title":"J. Med. Chem."},{"key":"2026090210483687500_cit12","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1039\/b719280k","article-title":"Nucleoside,\nNucleotide and Oligonucleotide Based Amphiphiles: A Successful Marriage\nof Nucleic Acids with Lipids","volume":"6","author":"Gissot","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"2026090210483687500_cit13","doi-asserted-by":"publisher","first-page":"5844","DOI":"10.1039\/c1cs15038c","article-title":"Hybrid Lipid\nOligonucleotide Conjugates: Synthesis, Self-Assemblies and Biomedical\nApplications","volume":"40","author":"Patwa","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"2026090210483687500_cit14","first-page":"276","article-title":"Lipid\nOligonucleotide Bioconjugates: Applications in Medicinal Chemistry","volume-title":"DNA in Supramolecular Chemistry and Nanotechnology","author":"Patwa","year":"2015"},{"key":"2026090210483687500_cit15","doi-asserted-by":"publisher","first-page":"3363","DOI":"10.1021\/ja01498a033","article-title":"The Synthesis of Nucleoside\nand Nucleotide Analogs Derived from Uridine*","volume":"82","author":"Bannister","year":"1960","journal-title":"J. Am. Chem. Soc."},{"key":"2026090210483687500_cit16","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1021\/ja00897a027","article-title":"The Structure and Properties\nof Some Sulfur Analogs\nof Acetoneuridine","volume":"85","author":"Chambers","year":"1963","journal-title":"J. Am. Chem. Soc."},{"key":"2026090210483687500_cit17","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1248\/cpb.20.193","article-title":"Formation and Characterization of\n5\u2032-Deoxy-5\u2032, 6-Epimino-5,\n6-Dihydro-2\u2032, 3\u2019-O-Isopropylideneuridine","volume":"20","author":"Isono","year":"1972","journal-title":"Chem. Pharm. Bull."},{"key":"2026090210483687500_cit18","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.1021\/ja01024a063","article-title":"Model Studies of\nThymidylate Synthetase. Neighboring-Group\nFacilitation of Electrophilic Substitution Reactions of Uracil Furanosides","volume":"90","author":"Santi","year":"1968","journal-title":"J. Am. Chem. 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Soc."},{"key":"2026090210483687500_cit22","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1055\/s-1994-25717","article-title":"A Novel\nRoute to Pyrimidine Nucleosides via Intramolecular Couplings of Bases\nwith 2\u2032-Deoxyribosides: Quick and Stereospecific...but with\na \u201cTwist\u201d","volume":"12","author":"Lipshutz","year":"1994","journal-title":"Synthesis"},{"key":"2026090210483687500_cit23","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.1016\/j.tet.2009.02.077","article-title":"Preparation\nof C5-Substituted O6,5\u2032-Cyclouridine","volume":"65","author":"Mieczkowski","year":"2009","journal-title":"Tetrahedron"},{"key":"2026090210483687500_cit24","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1039\/P19880002227","article-title":"Nucleosides. Part 5.\nIsolation and characterization of the stable cyclic adducts, (5R,6S)-\nand (5S,6S)-bromo-O6,5\u2032-cyclo-5,6-dihydrouridines in the bromination\nof 2\u2032,3\u2032-O-isopropylideneuridine with N-bromosuccinimide","volume":"1","author":"Hirota","year":"1988","journal-title":"J. Chem. Soc., Perkin Trans. 1"},{"key":"2026090210483687500_cit25","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1039\/C39840001658","article-title":"Reaction of Nucleosides\nwith Lead Tetra-Acetate: Facile Formation of Cyclonucleosides","volume":"24","author":"Kameyama","year":"1984","journal-title":"J. Chem. Soc., Chem. 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Acta, Nucleic Acids Protein Synth."},{"key":"2026090210483687500_cit31","doi-asserted-by":"publisher","first-page":"11630","DOI":"10.3390\/molecules171011630","article-title":"Recent Advances in\nCyclonucleosides: C-Cyclonucleosides\nand Spore Photoproducts in Damaged DNA","volume":"17","author":"Yoshimura","year":"2012","journal-title":"Molecules"},{"key":"2026090210483687500_cit32","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1021\/jo01026a008","article-title":"The Synthesis\nof Some 5\u2019-Thiopentofuranosylpyrimidines1","volume":"29","author":"Reist","year":"1964","journal-title":"J. Org. Chem."},{"key":"2026090210483687500_cit33","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1007\/s13361-012-0434-7","article-title":"Protonation Preferentially\nStabilizes Minor Tautomers\nof the Halouracils: IRMPD Action Spectroscopy and Theoretical Studies","volume":"23","author":"Crampton","year":"2012","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026090210483687500_cit34","doi-asserted-by":"publisher","first-page":"25978","DOI":"10.1039\/C5CP02227D","article-title":"Diverse Mixtures of 2,4-Dihydroxy\nTautomers and O4\nProtonated Conformers of Uridine and 2\u2032-Deoxyuridine Coexist\nin the Gas Phase","volume":"17","author":"Wu","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"2026090210483687500_cit35","doi-asserted-by":"publisher","first-page":"5076","DOI":"10.1021\/jo00200a010","article-title":"Cyclonucleoside Formation and Ring Cleavage in the Reaction of 2\u2032,3\u2019-O-Isopropylideneadenosine\nwith Benzoyl Chloride and Its Substituted Derivatives","volume":"49","author":"Anzai","year":"1984","journal-title":"J. Org. Chem."},{"key":"2026090210483687500_cit36","doi-asserted-by":"publisher","first-page":"172747","DOI":"10.1016\/j.ejphar.2019.172747","article-title":"Selected Nucleos(t)Ide-Based\nPrescribed Drugs and Their Multi-Target Activity","volume":"865","author":"Pastuch-Gawo\u0142ek","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"2026090210483687500_cit37","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1016\/0006-2952(85)90643-4","article-title":"5-Substituted-2,2\u2032-Anhydrouridines,\nPotent Inhibitors of Uridine Phosphorylase","volume":"34","author":"Veres","year":"1985","journal-title":"Biochem. Pharmacol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c03348","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/38\/24746\/67802542\/acsomega.0c03348.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/38\/24746\/67802542\/acsomega.0c03348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:49:27Z","timestamp":1788360567000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/38\/24746\/1372601\/Intramolecular-Michael-Additions-in-Uridine"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,15]]},"references-count":34,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2020,9,15]]},"published-print":{"date-parts":[[2020,9,29]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c03348","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,15]]}}}