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The suggested formation of this skeleton involves an in situ oximation\/dehydration\/SN\u2019 cascade reaction.<\/jats:p>","DOI":"10.3390\/molecules29225474","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T07:02:58Z","timestamp":1732086178000},"page":"5474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Unexpected Formation of Spiro Isoxazoline-Dihydrofurane Compounds from Substituted Ketofurfuryl Alcohols"],"prefix":"10.3390","volume":"29","author":[{"given":"Claire","family":"Cuyamendous","sequence":"first","affiliation":[{"name":"MSO, Institut des Mol\u00e9cules et Mat\u00e9riaux du Mans (IMMM), UMR CNRS 6283, Le Mans Universit\u00e9, Avenue O. 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Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e202103683","DOI":"10.1002\/chem.202103683","article-title":"Catalytic Reduction of Oximes to Hydroxylamines: Current Methods, Challenges and Opportunities","volume":"28","author":"Cramer","year":"2022","journal-title":"Chem. Eur. 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Topics in Heterocyclic Chemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1039\/D0OB00963F","article-title":"Recent advances in the oxime-participating synthesis of isoxazolines","volume":"18","author":"Liao","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rappoport, Z., and Liebman, J.F. (2009). Rearrangements of hydroxylamines, oximes and hydroxamic acids. Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids (Pt. 1), Wiley.","DOI":"10.1002\/9780470741962"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.2174\/1385272033486783","article-title":"1,3-Dipolar Cycloadditions in the Synthesis of Carbohydrate Mimics. Part 2: Nitrones and Oximes","volume":"7","author":"Koumbis","year":"2003","journal-title":"Curr. Org. Chem."},{"key":"ref_19","first-page":"377","article-title":"Therapeutic potential of 2-isoxazolines","volume":"66","author":"Imran","year":"2004","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1016\/S0040-4039(01)96202-1","article-title":"The isolation, structure, and absolute configuration of U-42,126 a novel antitumor antibiotic","volume":"14","author":"Martin","year":"1973","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejmech.2014.02.063","article-title":"Isoxazoline containing natural products as anticancer agents: A review","volume":"77","author":"Kaur","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1002\/tcr.202100032","article-title":"Anodic Oxidation of Phenols: A Key Step for the Synthesis of Natural Products","volume":"21","author":"Yamamoto","year":"2021","journal-title":"Chem. Rec."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"616","DOI":"10.2174\/157017911796957320","article-title":"Recent Advances in Nitrile Oxide Cycloadditions. Synthesis of Isoxazolines","volume":"8","author":"Rane","year":"2011","journal-title":"Curr. Org. Synth."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"628","DOI":"10.2174\/157017911796957393","article-title":"Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines","volume":"8","author":"Browder","year":"2011","journal-title":"Curr. Org. Synth."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1055\/s-0031-1290373","article-title":"Syntheses of isoxazoline-based amino acids by cycloaddition of nitrile oxides and their conversion into highly functionalized bioactive amino acid derivatives","volume":"44","author":"Kiss","year":"2012","journal-title":"Synthesis"},{"key":"ref_26","first-page":"e1800192","article-title":"Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin","volume":"352","author":"Pratap","year":"2019","journal-title":"Arch. Pharm. Chem. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rasool, J.U., Sawhney, G., Shaikh, M., Nalli, Y., Madishetti, S., Ahmed, Z., and Ali, A. (2021). Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B. Bioorganic Chem., 117.","DOI":"10.1016\/j.bioorg.2021.105408"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.1016\/S0040-4039(98)01903-0","article-title":"Cycloaddition\/Ring opening of 3-unsubstituted cyclic nitronates, isoxazoline and 5,6-dihydro-4H-1,2-oxazine N-oxides, as synthetic equivalents of functionalized nitrile oxides","volume":"39","author":"Kanemasa","year":"1998","journal-title":"Tetrahedron Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19704","DOI":"10.1021\/jacs.2c10010","article-title":"Total Synthesis of the Dihydrooxepine-Spiroisoxazoline Natural Product Psammaplysin A","volume":"144","author":"Paciorek","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1007\/s00044-016-1534-x","article-title":"Design, synthesis and biological evaluation of new tricyclic spiroisoxazoline derivatives as selective COX-2 inhibitors and study of their COX-2 binding modes via docking studies","volume":"25","author":"Abolhasani","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/BF00946676","article-title":"Rearrangements in the 6-nitro-2,9-dioxa-1-azabicyclo[4.3.0]nonane series","volume":"27","author":"Chlenov","year":"1978","journal-title":"Russ. Chem. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S0040-4039(98)02452-6","article-title":"A New access to spiro-isoxazolines derivatives","volume":"40","author":"Smietana","year":"1999","journal-title":"Tetrahedron Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.tetlet.2015.02.059","article-title":"Synthesis and investigation of novel spiro-isoxazolines as anti-cancer agents","volume":"56","author":"Das","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1002\/adsc.200600367","article-title":"Gold catalysis: Dihydroisobenzofurans and isochromanes by the intramolecular furan\/alkyne reaction","volume":"348","author":"Hashmi","year":"2006","journal-title":"Adv. Synth. Catal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9021","DOI":"10.1016\/j.tet.2009.08.074","article-title":"Gold catalysis: Benzanellation versus alkylidenecyclopentenone synthesis","volume":"65","author":"Hashmi","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1016\/S0040-4039(01)80480-9","article-title":"Synthesis of spiro and bicyclic nucleosides from ribose nitrile oxide with dimethyl acetylenedicarboxylate","volume":"30","author":"Yokoyama","year":"1989","journal-title":"Tetrahedron Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1093\/nar\/22.12.2430","article-title":"Removal of t-butyldimethylsilyl protection in RNA synthesis. Triethylamine trihydrofluoride (TEA, 3HF) is a more reliable alternative to tetrabutylammonium fluoride (TBAF)","volume":"22","author":"Westman","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1021\/acs.joc.6b00180","article-title":"Synthesis of isoxazoline\/cyclic nitrone-featured methylenes using unsaturated ketoximes: A dual role of TEMPO","volume":"81","author":"Chen","year":"2016","journal-title":"J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1021\/ja01368a056","article-title":"The preparation and properties of some new furan derivatives","volume":"52","author":"Peters","year":"1930","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tet.2017.11.054","article-title":"Chiral 2-(2-hydroxyaryl)alcohols (HAROLs) with a 1,4-diol scaffold as a new family of ligands and organocatalysts","volume":"74","author":"Dilek","year":"2018","journal-title":"Tetrahedron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5902","DOI":"10.1021\/ja00197a060","article-title":"Palladium-catalyzed trimethylenemethane reaction to form methylenetetrahydrofurans. Aldehyde and ketone substrates and the tin effect","volume":"111","author":"Trost","year":"1989","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5912","DOI":"10.1002\/anie.201402834","article-title":"Catalytic asymmetric synthesis of 8-oxabicyclooctanes by intermolecular [5+2] pyrylium cycloadditions","volume":"53","author":"Witten","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1021\/ja068901g","article-title":"Total syntheses of ipomoeassin B and E","volume":"129","author":"Nagano","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1055\/s-0032-1317520","article-title":"A concise total synthesis of (+)-cladospolide D","volume":"23","author":"Si","year":"2012","journal-title":"Synlett"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1021\/ol201604c","article-title":"Enantioselective formal synthesis of palmerolide A","volume":"13","author":"Prasad","year":"2011","journal-title":"Org. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"46","DOI":"10.15227\/orgsyn.095.0046","article-title":"Preparation of cyclopent-2-enone derivatives via the aza-Piancatelli rearrangement","volume":"95","author":"Nichol","year":"2018","journal-title":"Org. Synth."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1055\/s-0034-1379476","article-title":"An expeditious asymmetric synthesis of the polyketide unit present in HIV-inhibitory depsipeptides aetheramide A and B","volume":"25","author":"Revu","year":"2014","journal-title":"Synlett"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:36:00Z","timestamp":1760114160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":47,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["molecules29225474"],"URL":"https:\/\/doi.org\/10.3390\/molecules29225474","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}