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In particular, the clinical use of aminoglycoside antibiotics, broad\u2010spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram\u2010positive and Gram\u2010negative bacteria is phosphorylation of these amino sugars at the 3\u2019\u2010position by <jats:italic>O<\/jats:italic>\u2010phosphotransferases [APH(3\u2019)s]. Structural alteration of these antibiotics at the 3\u2019\u2010position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi\u2010step synthesis, which is not appealing for pharma industry in this low\u2010return\u2010on\u2010investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3\u2019)s, we introduce a novel regioselective modification of aminoglycosides in the 3\u2019\u2010position via palladium\u2010catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3\u2019)s\u2010mediated resistance employing only four synthetic steps.<\/jats:p>","DOI":"10.1002\/chem.202200883","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T02:49:49Z","timestamp":1649299789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Late\u2010Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3\u2019) Kinases"],"prefix":"10.1002","volume":"28","author":[{"given":"Andreas A.","family":"Bastian","sequence":"first","affiliation":[{"name":"Department of Chemical Biology Stratingh Institute for Chemistry  Nijenborgh 7 9747 AG Groningen (The Netherlands"},{"name":"AGILeBiotics B.V.  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