{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T07:01:04Z","timestamp":1762930864022,"version":"3.45.0"},"reference-count":91,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-90-04000"],"award-info":[{"award-number":["23-90-04000"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Risdiplam is the first approved small-molecule therapy for spinal muscular atrophy (SMA), a severe, progressive neuromuscular disorder. In addition to its clinical significance, risdiplam is of a great interest for organic and medicinal chemistry due to its complex molecular architecture. Its structure incorporates three highly substituted heterocyclic fragments\u2014imidazo[1,2-b]pyridazine, pyrido[1,2-a]pyrimidin-4-one, and 4,7-diazaspiro[2.5]octane\u2014that serve as both versatile synthetic building blocks and critical pharmacophoric elements for drug design and discovery. The increasing scientific interest in risdiplam has led to numerous publications and patent applications that describe alternative synthetic methodologies. Recently, our group has also developed and introduced efficient, scalable manufacturing routes for the preparation of the target substance and the key intermediates of its synthesis. This mini-review systematically analyzes a plethora of risdiplam assembly strategies and synthetic approaches, covering developments from 2013 to the present.<\/jats:p>","DOI":"10.3390\/molecules30224365","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:55:04Z","timestamp":1762930504000},"page":"4365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Risdiplam Synthesis Overview: From Cross-Coupling Reliance to Complete Palladium Independence"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-6942","authenticated-orcid":false,"given":"Georgiy","family":"Korenev","sequence":"first","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, 354340 Sirius, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5253-3706","authenticated-orcid":false,"given":"Maxim B.","family":"Nawrozkij","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, 354340 Sirius, Krasnodar Region, Russia"},{"name":"Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-4183","authenticated-orcid":false,"given":"Roman A.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, 354340 Sirius, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nishio, H., Niba, E.T.E., Saito, T., Okamoto, K., Takeshima, Y., and Awano, H. 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