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To expand the antibiotic pipeline,the strategy has focused on revitalizing the current antibiotic via novel site\u2010specific derivatization. Aminoglycosides (AGs), once considered effective therapeutics for treating clinical infections, are now used to a limited extent due to drug\u2010induced toxicity and AG\u2010resistant bacteria. Challenges in the synthesis and modification of AGs impede their potential for regain efficacy. Herein, a photoredox catalyzed late\u2010stage modification of glucosides including AGs is discussed. The chemistry can selectively install an alkyl group at the 3\u2010position of unprotected glucoside with a broad substrate scope and high yields. Among the products, a series of compounds are characterized that can overcome drug resistance caused by APH(3\u2032) and one of them achieves 30\u2010fold potency compared to kanamycin against sensitive strains. The chemistry described here opens a new avenue for discovering new AG antibiotics that overcome drug resistance and may also serve as the basis for understanding their structure\u2013activity relationships.<\/jats:p>","DOI":"10.1002\/cbic.202500320","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T04:16:56Z","timestamp":1761625016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Late\u2010Stage Functionalization of Glucosides and Aminoglycosides to Combat Resistant Resistance"],"prefix":"10.1002","volume":"26","author":[{"given":"Tianyun","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Product Chemistry Lanzhou University  Lanzhou 730000 P. R. 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