Palladium-Catalyzed Enantioselective Arylative Dearomatization of Naphthols and Phenols for Constructing Quinazoline-Containing Spirocycles
文献类型：期刊论文
| 作者 | Zhang, Chiyue5; Xu, Gaoya1,3,5,6; Zhao, Wenlu5; Li, Xutong4,6; Zheng, Mingyue4,6 ; Zhou, Yubo1,2,4,5,6; Li, Jia1,2,3,4,5,6; Li, Qi4,5,6
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| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2025-05-15 |
| 页码 | 9 |
| 关键词 | Antiproliferative activity Catalytic asymmetric dearomatization Palladium Quinazoline-containing spirocycles Three-dimensionality |
| DOI | 10.1002/anie.202503359 |
| 通讯作者 | Li, Jia(jli@simm.ac.cn) ; Li, Qi(qi.li@simm.ac.cn) |
| 英文摘要 | We report a palladium-catalyzed 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-containing spirocyclic compounds, featuring enantioenriched, three-dimensional molecular architectures through the strategic integration of quinazolinone and spirocyclic frameworks. The successful transformation of planar aromatic precursors into complex three-dimensional 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 MV4-11 (human acute myeloid leukemia), revealing that compound (S)-4ac, characterized by well-defined stereochemistry and structural novelty, exhibited significantly enhanced antiproliferative efficacy against both cancer cell lines, with IC50 values 0.9 mu M and 0.5 mu M, 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 (S)-4ac as a highly promising lead compound for further anticancer drug development. |
| WOS关键词 | ASYMMETRIC DEAROMATIZATION ; INTRAMOLECULAR DEAROMATIZATION ; LIGANDS ; SPIROLACTONIZATION ; PHOSPHORAMIDITES ; CYCLIZATION |
| 资助项目 | Shanghai Institute of Material Medica (SIMM), Science and Technology Commission of Shanghai Municipality[23ZR1474800] ; National Natural Science Foundation of China (NSFC) Excellent Young Scholars Fund (overseas), startup funding from the Shanghai Institute of Material Medica (SIMM), Science and Technology Commission of Shanghai Municipality[21PJ1415500] ; Shanghai Pujiang Program |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001488038900001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317929]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Jia; Li, Qi |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Chiyue,Xu, Gaoya,Zhao, Wenlu,et al. Palladium-Catalyzed Enantioselective Arylative Dearomatization of Naphthols and Phenols for Constructing Quinazoline-Containing Spirocycles[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025:9. |
| APA | Zhang, Chiyue.,Xu, Gaoya.,Zhao, Wenlu.,Li, Xutong.,Zheng, Mingyue.,...&Li, Qi.(2025).Palladium-Catalyzed Enantioselective Arylative Dearomatization of Naphthols and Phenols for Constructing Quinazoline-Containing Spirocycles.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,9. |
| MLA | Zhang, Chiyue,et al."Palladium-Catalyzed Enantioselective Arylative Dearomatization of Naphthols and Phenols for Constructing Quinazoline-Containing Spirocycles".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2025):9. |
入库方式： OAI收割
来源：上海药物研究所
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