{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:16:45Z","timestamp":1788466605703,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministry for Universities and Research","doi-asserted-by":"publisher","award":["2022KMS84P"],"award-info":[{"award-number":["2022KMS84P"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemSusChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Indirubin, the active component of the traditional Chinese remedy\n                    <jats:italic>Dang Gui Long Hui Wan<\/jats:italic>\n                    , exhibits broad therapeutic potential. However, its scalable and sustainable synthesis remains challenging when using conventional methods. We report a green and efficient synthetic protocol using deep eutectic solvents (DESs) as environmentally benign media. Indirubin was synthesized from isatin using NaBH\n                    <jats:sub>4<\/jats:sub>\n                    in a choline chloride\/urea DES at 70\u00b0C under air, achieving a 70% overall yield in 24 h without chromatographic purification. This approach, combined with an optimized work\u2010up, significantly reduces organic solvent use, improving both process safety and environmental sustainability. The protocol is robust and scalable, as demonstrated by a pilot\u2010scale preparation (386 g of isatin in 1.94\u2009kg of DES), and grants access to a variety of indirubin derivatives, such as 5,5\u2032\u2010difluoro, 5,5\u2032\u2010dibromo, 5,5\u2032\u2010dimethoxy, 5,5\u2032\u2010dimethyl, 5\u2010bromoindirubin, 3\u2032\u2010oxime, and\n                    <jats:italic>N<\/jats:italic>\n                    \u2010alkylated analogs, the latter being of particular interest as photoswitchable molecular platforms. A comprehensive CHEM21 metrics assessment reveals a 3.7\u2010fold reduction in E\u2010factor and improved effective mass yield (EM) and process mass intensity (PMI) values compared to conventional methanol\u2010based methods, underscoring the reduced environmental footprint of this approach. Overall, this strategy provides a greener, safer, and industrially viable route to pharmaceutically relevant indirubin scaffolds, fully aligned with sustainable chemistry principles.\n                  <\/jats:p>","DOI":"10.1002\/cssc.202502114","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:31:52Z","timestamp":1765197112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Scalable and Sustainable Synthesis of Indirubin Frameworks Enabled by Deep Eutectic Solvents"],"prefix":"10.1002","volume":"19","author":[{"given":"Biagio","family":"Delvecchio","sequence":"first","affiliation":[{"name":"Dipartimento di Farmacia\u2013Scienze del Farmaco Universit\u00e0 degli Studi di Bari Aldo Moro, Consorzio CINMPIS  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-3993","authenticated-orcid":false,"given":"Luciana","family":"Cicco","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia\u2013Scienze del Farmaco Universit\u00e0 degli Studi di Bari Aldo Moro, Consorzio CINMPIS  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-9106","authenticated-orcid":false,"given":"Andrea Nicola","family":"Paparella","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia\u2013Scienze del Farmaco Universit\u00e0 degli Studi di Bari Aldo Moro, Consorzio CINMPIS  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Di Salvo","sequence":"additional","affiliation":[{"name":"Dieffetti Cosmetici S.r.l.  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