{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:02:41Z","timestamp":1790132561158,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"27","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We report a palladium\u2010catalyzed enantioselective arylative dearomatization of phenols and naphthols, demonstrating a broad substrate scope and excellent functional group tolerance. This approach enables the efficient construction of a diverse library of quinazoline\u2010containing spirocyclic compounds, featuring enantioenriched, three\u2010dimensional molecular architectures through the strategic integration of quinazolinone and spirocyclic frameworks. The successful transformation of planar aromatic precursors into complex three\u2010dimensional molecular architectures using our developed methodology was further validated by principal moment of inertia (PMI) calculations. Additionally, we systematically evaluated the antiproliferative potential of the synthesized compounds against two representative cancer cell lines: Mino (human mantle cell lymphoma) and MV4\u201011 (human acute myeloid leukemia), revealing that compound (\n                    <jats:bold>\n                      <jats:italic>S<\/jats:italic>\n                      )\u20104ac,\n                    <\/jats:bold>\n                    characterized by well\u2010defined stereochemistry and structural novelty, exhibited significantly enhanced antiproliferative efficacy against both cancer cell lines, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values 0.9\u00a0\u00b5M and 0.5\u00a0\u00b5M, respectively. In addition, flow cytometry quantification and western blot analysis showed that these compounds induced apoptosis through caspase activation and mitochondrial dysfunction. These results demonstrated\n                    <jats:bold>\n                      (\n                      <jats:italic>S<\/jats:italic>\n                      )\u20104ac\n                    <\/jats:bold>\n                    as a highly promising lead compound for further anticancer drug development.\n                  <\/jats:p>","DOI":"10.1002\/anie.202503359","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T03:55:26Z","timestamp":1745898926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Palladium\u2010Catalyzed Enantioselective Arylative Dearomatization of Naphthols and Phenols for Constructing Quinazoline\u2010Containing Spirocycles"],"prefix":"10.1002","volume":"64","author":[{"given":"Chiyue","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoya","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"The National Center for Drug Screening, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xutong","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Zhongshan 528400 China"},{"name":"The National Center for Drug Screening, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"},{"name":"State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Zhongshan 528400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24224165"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01473"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116270"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901241e"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.8b03694"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2025.130096"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201204822"},{"key":"e_1_2_5_8_1","first-page":"229","volume-title":"Asymmetric Dearomatization Reactions","author":"Bedford R. B."},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2016.11.005"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2018.06.006"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NP00098K"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00436F"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.0c01651"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44160-022-00039-y"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200907352"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201303559"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja401074u"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200800464"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-021-00778-z"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202207518"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202309256"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja203644q"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja508645j"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201411817"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC01859B"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b00783"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.202000109"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c05008"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202303639"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c10663"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202403664"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201100206"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b01707"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b01285"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b04813"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c09638"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c02550"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.31635\/ccschem.021.202100831"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.4c01563"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-024-01608-8"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c14754"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.03.076"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01122"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904948"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c05535"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20020703)41:13<2348::AID-ANIE2348>3.0.CO;2-K"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar700137z"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.6b01001"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.9b00029"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.4c00064"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0pp00034e"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2024.108911"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.202201333"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci025599w"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa920"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202503359","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202503359","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202503359","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:47:08Z","timestamp":1772959628000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202503359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":55,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/anie.202503359"],"URL":"https:\/\/doi.org\/10.1002\/anie.202503359","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]},"assertion":[{"value":"2025-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202503359"}}