{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:03:43Z","timestamp":1790784223047,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"40","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374155"],"award-info":[{"award-number":["82374155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22371021"],"award-info":[{"award-number":["22371021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heteroaromatic <jats:italic>N<\/jats:italic>\u2010oxides, renowned for their highly polar N\u2500O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic <jats:italic>N<\/jats:italic>\u2010oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic <jats:italic>N<\/jats:italic>\u2010oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu\u2010catalyzed atroposelective method for synthesizing biaryl <jats:italic>N<\/jats:italic>\u2010oxides via <jats:italic>de novo<\/jats:italic> heteroaromatic <jats:italic>N<\/jats:italic>\u2010oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of <jats:italic>N<\/jats:italic>\u2010oxides with novel heteroaromatic scaffolds. The axially chiral <jats:italic>N<\/jats:italic>\u2010oxide product <jats:bold>3f<\/jats:bold> demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product <jats:bold>3e<\/jats:bold> exhibits promising therapeutic efficacy against triple\u2010negative breast cancer, with IC<jats:sub>50<\/jats:sub> values of 4.8 and 5.2\u00a0\u00b5<jats:sc>m<\/jats:sc> in MDA\u2010MB\u2010231 and MDA\u2010MB\u2010468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic <jats:italic>N<\/jats:italic>\u2010oxides but also encourages further exploration of <jats:italic>N<\/jats:italic>\u2010oxide entities in the discovery of bioactive small molecules.<\/jats:p>","DOI":"10.1002\/advs.202405743","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T08:27:10Z","timestamp":1723192030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Atroposelective Synthesis of Biaryl <i>N<\/i>\u2010Oxides via Cu\u2010Catalyzed De Novo Heteroaromatic <i>N<\/i>\u2010Oxide Ring Formation"],"prefix":"10.1002","volume":"11","author":[{"given":"Ke","family":"Ma","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Qi","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Agent Creation Engineering Research Centre of Sichuan Province Sichuan Industrial Institute of Antibiotics School of Pharmacy Chengdu University  Chengdu 610106 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"},{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Long","family":"Li","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Agent Creation Engineering Research Centre of Sichuan Province Sichuan Industrial Institute of Antibiotics School of Pharmacy Chengdu University  Chengdu 610106 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8263","authenticated-orcid":false,"given":"Gu","family":"Zhan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-4682","authenticated-orcid":false,"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600640822"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1159\/000211131"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12504905"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666150619104007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01332"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00442"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2021.1945527"},{"key":"e_1_2_8_3_4","doi-asserted-by":"publisher","DOI":"10.1021\/jm0155401"},{"key":"e_1_2_8_3_5","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(01)00163-8"},{"key":"e_1_2_8_3_6","doi-asserted-by":"publisher","DOI":"10.1021\/jm061232x"},{"key":"e_1_2_8_3_7","doi-asserted-by":"publisher","DOI":"10.1038\/345346a0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00254"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0101914"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr020050h"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17472"},{"key":"e_1_2_8_5_4","doi-asserted-by":"publisher","DOI":"10.1021\/ar200015s"},{"key":"e_1_2_8_5_5","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.7b00377"},{"key":"e_1_2_8_5_6","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.201800155"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200600474"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25020330"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201812864"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201700977"},{"key":"e_1_2_8_7_3","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c04923"},{"key":"e_1_2_8_7_4","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c09075"},{"key":"e_1_2_8_7_5","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.2c01924"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja981091r"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo015593q"},{"key":"e_1_2_8_8_3","doi-asserted-by":"publisher","DOI":"10.1021\/ja025670e"},{"key":"e_1_2_8_8_4","doi-asserted-by":"publisher","DOI":"10.1021\/ol026376u"},{"key":"e_1_2_8_8_5","doi-asserted-by":"publisher","DOI":"10.1021\/jo034603f"},{"key":"e_1_2_8_8_6","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200404054"},{"key":"e_1_2_8_8_7","doi-asserted-by":"publisher","DOI":"10.1039\/C6CC04816A"},{"key":"e_1_2_8_8_8","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b02457"},{"key":"e_1_2_8_8_9","doi-asserted-by":"publisher","DOI":"10.1007\/s00706-018-2289-5"},{"key":"e_1_2_8_8_10","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b01687"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/cs500813z"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.3c01385"},{"key":"e_1_2_8_9_3","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b10414"},{"key":"e_1_2_8_9_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22621-2"},{"key":"e_1_2_8_9_5","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b04151"},{"key":"e_1_2_8_9_6","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202203051"},{"key":"e_1_2_8_9_7","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201605486"},{"key":"e_1_2_8_9_8","doi-asserted-by":"publisher","DOI":"10.1007\/s11426-022-1402-9"},{"key":"e_1_2_8_9_9","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202312923"},{"key":"e_1_2_8_9_10","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.4c01886"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44160-022-00114-4"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40978-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202312663"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01306"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.2c00486"},{"key":"e_1_2_8_12_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2022.04.011"},{"key":"e_1_2_8_12_4","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c00462"},{"key":"e_1_2_8_12_5","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c13538"},{"key":"e_1_2_8_12_6","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202116829"},{"key":"e_1_2_8_12_7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29557-1"},{"key":"e_1_2_8_12_8","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202214460"},{"key":"e_1_2_8_12_9","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202305067"},{"key":"e_1_2_8_12_10","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202302749"},{"key":"e_1_2_8_12_11","doi-asserted-by":"publisher","DOI":"10.1038\/s41929-022-00831-1"},{"key":"e_1_2_8_12_12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27771-x"},{"key":"e_1_2_8_12_13","doi-asserted-by":"publisher","DOI":"10.1039\/D3CC01705B"},{"key":"e_1_2_8_12_14","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2021.11.015"},{"key":"e_1_2_8_12_15","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310004"},{"key":"e_1_2_8_12_16","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202211977"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114700"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.2c00485"},{"key":"e_1_2_8_13_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.2c00500"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01260-0"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18794-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106696"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00573J"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202405743","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:08:27Z","timestamp":1759784907000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202405743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":71,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/advs.202405743"],"URL":"https:\/\/doi.org\/10.1002\/advs.202405743","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,9]]},"assertion":[{"value":"2024-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2405743"}}