{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:58:45Z","timestamp":1760147925630,"version":"build-2065373602"},"reference-count":11,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:00:00Z","timestamp":1678579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT national funds","award":["UIDB\/50006\/2020","UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020","UIDP\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molbank"],"abstract":"<jats:p>Voriconazole (VN) is an antifungal drug indicated for the treatment of several fungal infections. Due to its side effects, some works involving late-stage functionalization of VN have been reported in the literature. Here, we disclose a new VN derivative, the 6-[(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5-fluoropyrimidine-4-carbaldehyde (VN-CHO). This compound results from the photoredox-catalyzed hydroxymethylation of VN, affording a hydroxymethylated derivative (VN-CH2OH), followed by oxidation of the former CH2OH group. VN-CHO was obtained in good yield (70% yield) and its structure was unveiled by 1D (1H and 13C) and 2D (HSQC and HMBC) NMR techniques. The introduction of a formyl group in VN structure creates a very promising site for further functionalization in a molecule which originally does not have many active sites.<\/jats:p>","DOI":"10.3390\/m1603","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T06:52:13Z","timestamp":1678690333000},"page":"M1603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["6-[(2S,3R)-3-(2,4-Difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5-fluoropyrimidine-4-carbaldehyde"],"prefix":"10.3390","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-4197","authenticated-orcid":false,"given":"Joana L. C.","family":"Sousa","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-3316","authenticated-orcid":false,"given":"H\u00e9lio M. T.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-8286","authenticated-orcid":false,"given":"Artur M. S.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/1469-0691.12513","article-title":"Update on antifungal resistance in Aspergillus and Candida","volume":"20","author":"Arendrup","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"126951","DOI":"10.1016\/j.bmcl.2020.126951","article-title":"Design, synthesis, and structure-activity relationship studies of novel triazole agents with strong antifungal activity against Aspergillus fumigatus","volume":"30","author":"Ding","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Garcia-Effron, G. (2021). Molecular Markers of Antifungal Resistance: Potential Uses in Routine Practice and Future Perspectives. J. Fungi, 7.","DOI":"10.3390\/jof7030197"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104240","DOI":"10.1016\/j.bioorg.2020.104240","article-title":"History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action","volume":"104","author":"Shafiei","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114161","DOI":"10.1016\/j.ejmech.2022.114161","article-title":"Synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole in the antifungal drug development","volume":"231","author":"Ghobadi","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/op0000879","article-title":"Process Development of Voriconazole:\u2009 A Novel Broad-Spectrum Triazole Antifungal Agent","volume":"5","author":"Butters","year":"2001","journal-title":"Org. Process Res. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3797\/scipharm.1501-13","article-title":"Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole","volume":"83","author":"Sundaram","year":"2015","journal-title":"Sci. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1080\/17460441.2019.1653850","article-title":"An overview of late-stage functionalization in today\u2019s drug discovery","volume":"14","author":"Moir","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1039\/C5CS00628G","article-title":"The medicinal chemist\u2019s toolbox for late stage functionalization of drug-like molecules","volume":"45","author":"Cernak","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6898","DOI":"10.1021\/acs.joc.6b01449","article-title":"Photoredox Catalysis in Organic Chemistry","volume":"81","author":"Shaw","year":"2016","journal-title":"J. Org. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6980","DOI":"10.1021\/acs.joc.6b00811","article-title":"Photoredox-Catalyzed Hydroxymethylation of Heteroaromatic Bases","volume":"81","author":"Huff","year":"2016","journal-title":"J. Org. Chem."}],"container-title":["Molbank"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-8599\/2023\/1\/M1603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:53:22Z","timestamp":1760122402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-8599\/2023\/1\/M1603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,12]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["M1603"],"URL":"https:\/\/doi.org\/10.3390\/m1603","relation":{},"ISSN":["1422-8599"],"issn-type":[{"type":"electronic","value":"1422-8599"}],"subject":[],"published":{"date-parts":[[2023,3,12]]}}}