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Levoglucosenone, a cellulose\u2010derived platform molecule, provides access to structurally distinctive bicyclic acetals with considerable relevance in medicinal chemistry. In this study, we investigated the synthesis and antifungal properties of novel isothiocyanate derivatives incorporating the 6,8\u2010dioxabicyclo[3.2.1]octene scaffold. A synthetic approach based on the introduction of a thiocyanate group, followed by a [3,3]\u2010sigmatropic rearrangement, enabled the efficient preparation of two isothiocyanate derivatives. Optimization of reaction conditions led to improved yields, while comprehensive structural characterization confirmed the regio\u2010 and stereoselective nature of the transformations. Biological evaluation demonstrated broad\u2010spectrum antifungal activity against clinically relevant pathogens, including\n                    <jats:italic>Candida<\/jats:italic>\n                    ,\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    ,\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    , and dermatophytes, with compound\n                    <jats:bold>7<\/jats:bold>\n                    consistently exhibiting superior potency. Both compounds displayed fungicidal activity and effectively inhibited key virulence factors at sub\u2010inhibitory concentrations. In particular, they impaired\n                    <jats:italic>Candida<\/jats:italic>\n                    <jats:italic>albicans<\/jats:italic>\n                    morphogenesis and suppressed urease activity and melanin production in\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    species, without affecting capsule formation. These findings underscore the potential of levoglucosenone\u2010derived isothiocyanates as promising scaffolds for antifungal drug development, combining potent growth inhibition with the ability to disrupt critical pathogenic mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70357","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T03:25:37Z","timestamp":1782530737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Levoglucosenone\u2010Derived Isothiocyanates as Antifungal Compounds: Merging Sustainability and Medicinal Chemistry"],"prefix":"10.1002","volume":"21","author":[{"given":"Florencia","family":"C\u00e1mpora","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Instituto de Qu\u00edmica Rosario Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario \u2013 CONICET  Rosario 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y Farmac\u00e9uticas, Universidad Nacional de Rosario \u2013 CONICET  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-0306","authenticated-orcid":false,"given":"Ariel M.","family":"Sarotti","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Instituto de Qu\u00edmica Rosario Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario \u2013 CONICET  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-383X","authenticated-orcid":false,"given":"Camilla","family":"Matassini","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u2018Ugo Schiff\u2019 (DICUS) Universit\u00e0 degli Studi di Firenze  Sesto Fiorentino Florence 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