{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:01:39Z","timestamp":1792627299563,"version":"4.5.0"},"reference-count":110,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Compounds bearing the phosphorus\u2013carbon (P\u2013C) bond have important pharmacological, biochemical, and toxicological properties. Historically, the most notable reaction for the formation of the P\u2013C bond is the Michaelis\u2013Arbuzov reaction, first described in 1898. The classical Michaelis\u2013Arbuzov reaction entails a reaction between an alkyl halide and a trialkyl phosphite to yield a dialkylalkylphosphonate. Nonetheless, deviations from the classical mechanisms and new modifications have appeared that allowed the expansion of the library of reactants and consequently the chemical space of the yielded products. These involve the use of Lewis acid catalysts, green methods, ultrasound, microwave, photochemically-assisted reactions, aryne-based reactions, etc. Here, a detailed presentation of the Michaelis\u2013Arbuzov reaction and its developments and applications in the synthesis of biomedically important agents is provided. Certain examples of such applications include the development of alkylphosphonofluoridates as serine hydrolase inhibitors and activity-based probes, and the P\u2013C containing antiviral and anticancer agents.<\/jats:p>","DOI":"10.3390\/ijms23063395","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"3395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Improvements, Variations and Biomedical Applications of the Michaelis\u2013Arbuzov Reaction"],"prefix":"10.3390","volume":"23","author":[{"given":"Stavroula","family":"Kostoudi","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy-Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-4292","authenticated-orcid":false,"given":"Georgios","family":"Pampalakis","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy-Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sadowski, L.A., Upadhyay, R., Greeley, Z.W., and Margulies, B.J. 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