{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:57:34Z","timestamp":1793289454429,"version":"4.5.0"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"49","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,12,9]]},"abstract":"<jats:p>Radical-mediated 1,2-difunctionalization of olefins is a well-established synthetic technique widely used in the rapid construction of structurally diverse molecular entities. However, radical-mediated 1,3-difunctionalization reactions are rare, and the substrates are generally limited to strained skeletons. Here, we report a practical approach for 1,3-difunctionalization of available \u03b2,\u03b3-unsaturated ketones via a radical cascade process including visible light\u2013irradiated radical addition, thermodynamic stability\u2013driven 1,2-carbonyl migration from unactivated all-carbon quaternary center, and terminal C-radical varied transformations. Various highly functionalized alkyl skeletons with different valuable functional groups at positions 1 and 3 and the carbonyl group at position 2 have been synthesized through a radical chain pathway or Cu-catalyzed Ritter-type reaction. Moreover, this protocol provides a real case of diversity-oriented radical rearrangement for drug discovery. We identified a previously unknown chemotype of dual inhibitors for hypoxia-inducible factor (HIF) and WNT signaling pathways from products. These small-molecule inhibitors could suppress HIF and WNT signaling\u2013dependent HCT116 cell growth in 2D and 3D culture systems.<\/jats:p>","DOI":"10.1126\/sciadv.abq8596","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T18:58:20Z","timestamp":1670612300000},"source":"Crossref","is-referenced-by-count":42,"title":["Visible light\u2013initiated radical 1,3-difunctionalization of \u03b2,\u03b3-unsaturated ketones"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-1581","authenticated-orcid":true,"given":"Ruihua","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, P.\u00a0R.\u00a0China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, P.\u00a0R.\u00a0China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, P.\u00a0R.\u00a0China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zemin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, P.\u00a0R.\u00a0China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-5633","authenticated-orcid":true,"given":"Xiangqian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, 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