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Leveraging a deconstruction strategy, the rifamycin ansa chain can be isolated and selectively modified to reveal a hydroxyl group at O6, providing a handle for structural diversification. In parallel, a synthesis of the naphthoquinone core, highlighted by a biomimetic oxidative cyclization of a polypropionate precursor, furnished the complete C1\u2013C13 fragment. Reunion of these fragments provided a new rifamycin analog, denoted rifalene M, in which the synthetically challenging enol ether motif is replaced with a simple allylic linkage and retains antimicrobial activity.<\/jats:p>","DOI":"10.1021\/jacs.6c07977","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T01:01:47Z","timestamp":1786582907000},"page":"35245-35249","source":"Crossref","is-referenced-by-count":0,"title":["A Pull-Apart Strategy\nfor Synthetic Rifamycins"],"prefix":"10.1021","volume":"148","author":[{"given":"Mark","family":"Mahoney","sequence":"first","affiliation":[{"name":"University of Utah , , 315 S 1400 E , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell L.","family":"Ellinwood","sequence":"additional","affiliation":[{"name":"University of Utah , , 315 S 1400 E , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Landward","sequence":"additional","affiliation":[{"name":"University of Utah , , 315 S 1400 E , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-1363","authenticated-orcid":true,"given":"Ryan E.","family":"Looper","sequence":"additional","affiliation":[{"name":"University of Utah , , 315 S 1400 E , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"2","key":"2026090104495647900_cit1","first-page":"146","article-title":"Rifomycin, a new antibiotic; preliminary\nreport","volume":"14","author":"Sensi","year":"1959","journal-title":"Farmaco Sci."},{"issue":"5","key":"2026090104495647900_cit2","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1159\/000220462","article-title":"Rifampicin: a new orally\nactive rifamycin","volume":"11","author":"Maggi","year":"1966","journal-title":"Chemotherapia"},{"issue":"Supplement_3","key":"2026090104495647900_cit3","doi-asserted-by":"publisher","first-page":"S402","DOI":"10.1093\/clinids\/5.Supplement_3.S402","article-title":"History of\nthe Development of Rifampin","volume":"5","author":"Sensi","year":"1983","journal-title":"Rev. of Infect.\nDis."},{"key":"2026090104495647900_cit4","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1159\/000386837","article-title":"Chemical and\nbiological properties of rifampicin","volume":"16","author":"Furesz","year":"1970","journal-title":"Antibiot.\nChemother."},{"issue":"2","key":"2026090104495647900_cit5","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.tube.2010.02.001","article-title":"Rifamycins\n\u2013 Obstacles and opportunities","volume":"90","author":"Aristoff","year":"2010","journal-title":"Tuberculosis"},{"issue":"2","key":"2026090104495647900_cit6","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1021\/cr030112j","article-title":"Rifamycin-mode of action, resistance, and biosynthesis","volume":"105","author":"Floss","year":"2005","journal-title":"Chem. 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