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光氧化还原催化的氨基甲酰基自由基引发的去芳构化螺环化反应合成螺环环己二烯氧化吲哚。

Photoredox-Catalyzed Carbamoyl Radical-Initiated Dearomative Spirocyclization To Access Spiro-Cyclohexadiene Oxindoles.

作者信息

Ma Chunhua, Guo Qing, Meng Hui, Yan Shengnan, Ding Qingjie, Jiang Yuqin, Yu Bing

机构信息

Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Research Centre of Chiral Hydroxyl Pharmaceutical, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.

College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.

出版信息

Org Lett. 2024 Oct 11;26(40):8503-8508. doi: 10.1021/acs.orglett.4c03045. Epub 2024 Oct 1.

Abstract

The sustainable construction of spirocyclic compounds is important to the scientific community and the pharmaceutical industries. Herein, we demonstrate a carbamoyl radical-initiated intramolecular dearomative spirocyclization to access the spiro-cyclohexadiene oxindoles under visible light irradiation, which constitutes the first example of accessing the I-substituted derivatives that facilitate diversified transformations. Additionally, the scalability, late-stage modification of drugs, and significant antitumor activity of the products demonstrate the novel spirocyclic synthesis platform for expediting drug development.

摘要

螺环化合物的可持续构建对科学界和制药行业都很重要。在此,我们展示了一种在可见光照射下,由氨基甲酰基自由基引发的分子内脱芳构化螺环化反应,用于合成螺环环己二烯氧化吲哚,这是合成便于进行多样化转化的I-取代衍生物的首个实例。此外,该反应的可扩展性、药物的后期修饰以及产物显著的抗肿瘤活性,都证明了这是一个加速药物开发的新型螺环合成平台。

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