{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:16:22Z","timestamp":1766553382027,"version":"3.48.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008389","name":"Minister of Science and Higher Education","doi-asserted-by":"crossref","award":["SKN\/SP\/602501\/2024"],"award-info":[{"award-number":["SKN\/SP\/602501\/2024"]}],"id":[{"id":"10.13039\/100008389","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009045","name":"Jagiellonian University Medical College","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tecovirimat is an antiviral agent approved for the treatment of orthopoxvirus infections including smallpox, cowpox and monkeypox. A key challenge in its synthesis lies in the generation of maleimide intermediates, which traditionally requires high-temperature thermal rearrangement and often results in low-to-moderate yields. Classical methods rely on heating in toluene above 70 \u00b0C, limiting scalability and efficiency. Herein, we present a mild and efficient organocatalytic approach to the synthesis of tecovirimat intermediates, using a room-temperature Mumm rearrangement of isomaleimide precursors. The reaction is catalyzed by 10 mol% imidazole and N-hydroxysuccinimide. As a representative example for one of the tecovirimat synthesis methods, intermediate N-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4-(trifluoromethyl)benzamide was synthesized from p-trifluoromethylbenzohydrazide at a 71% yield over two steps. Additionally, N-(2,5-dioxopyrrol-1-yl)(tert-butoxy)formamide was obtained from Boc-hydrazide at a 37% yield. The methodology was sufficiently extended to other benzohydrazide-derived isomaleimides. To support the mechanistic rationale, preliminary PM7 semiempirical computational studies were performed, highlighting the electronic features facilitating the transformation. This work offers a practical and scalable route to tecovirimat intermediates, overcoming key synthetic bottlenecks and enhancing the efficiency of antiviral drug production.<\/jats:p>","DOI":"10.3390\/ijms27010061","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:27:47Z","timestamp":1766500067000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of Antiviral Drug Tecovirimat and Its Key Maleimide Intermediates Using Organocatalytic Mumm Rearrangement at Ambient Conditions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-809X","authenticated-orcid":false,"given":"Przemys\u0142aw W.","family":"Szafra\u0144ski","sequence":"first","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3691-5627","authenticated-orcid":false,"given":"Wojciech","family":"Tryba\u0142a","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"},{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 16 \u0141azarza Street, 31-530 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Mazur","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4132-2877","authenticated-orcid":false,"given":"Katarzyna","family":"Pa\u0144czyk-Straszak","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Kacprzak","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-7982","authenticated-orcid":false,"given":"Vittorio","family":"Canale","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6192-8721","authenticated-orcid":false,"given":"Pawe\u0142","family":"Zajdel","sequence":"additional","affiliation":[{"name":"Chair of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meyer, H., Ehmann, R., and Smith, G.L. 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