卤键促进的2-溴丙腈衍生物与香豆素/喹啉酮的交叉偶联反应：合成与转化

doi:10.6023/cjoc202504009

有机化学

研究论文

卤键促进的2-溴丙腈衍生物与香豆素/喹啉酮的交叉偶联反应：合成与转化

温吉林^a, 郭鹏^a, 蒲国良^a, 满雪玉^b,*, 贺春阳^a,*

^a贵州省化学药物创新全省重点实验室遵义医科大学药学院遵义 563000;
^b湖南医药学院第一附属医院基层数字医防一体化工程技术研究中心

收稿日期:2025-04-08 修回日期:2025-06-05
基金资助:
国家自然科学基金(项目编号：22461050、22161054)和贵州省科学技术厅 (黔科合平台人才-CXTD[2022]012) 资助项目.

Halogen-Bond-Promoted Direct Cross-Coupling of 2-Bromopropionitrile derivatives with Coumarins/Quinolinones: Synthesis and Transformation

Wen, Jilin^a, Guo, Peng^a, Pu, Guoliang^a, Man, Xueyu^b,*, He Chun-Yang^a,*

^aGuizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, School of Pharmacy Zunyi Medical University Zunyi 563000

Received:2025-04-08 Revised:2025-06-05
Contact: *E-mail:hechy2002@163.com,xueyu_man@foxmail.com
Supported by:
National Natural Science Foundation of China (No. 22461050, 22161054), and Science and Technology Department of Guizhou Province (No. QKHPTRC-CXTD2022-012).

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摘要/Abstract

本文开发了一种由卤键促进的 2-溴丙腈衍生物与香豆素/喹啉酮类化合物的交叉偶联反应。该方法反应体系简单,反应条件温和,并能以中等至良好的收率获得目标产物。得到的目标化合物中的氰基官能团可在温和条件下高效转化为 2H-四唑衍生物。我们使用酯类类似物进行了对比研究,结果显示其反应活性相较于氰基对应物显著降低,这凸显了氰基在该转化过程中的重要作用。初步细胞实验表明,化合物4b选择性地杀伤MDA-MB-231细胞,其IC₅₀值为22.8±1.3 μM,其他多数化合物对肿瘤细胞和HL-7702正常细胞均表现出无毒或者较低毒性,这些初步的活性结果为后续对于其他生物活性如抗氧化活性、抗菌活性的研究提供了基础。

关键词: 卤键, 香豆素/喹啉酮, 2-溴丙腈衍生物, 偶联反应

This study reports a halogen bond-promoted cross-coupling reaction between 2-bromopropionitrile derivatives and coumarin/quinolinone compounds. The developed methodology features a simple reaction system, mild conditions, and provides target products in moderate to good yields. The cyano functional group in the obtained compounds could be efficiently converted into 2H-tetrazole derivatives under mild conditions. Comparative studies using ester analogs demonstrated significantly reduced reactivity compared to their cyano counterparts, highlighting the crucial role of the cyano group in this transformation. Preliminary cellular experiments revealed that compound 4b selectively inhibited MDA-MB-231 cells with an IC₅₀ value of 22.8±1.3 μM, while most other compounds exhibited non-toxic or low toxicity toward both tumor cells and HL-7702 normal cells. These findings establish a foundation for further investigations into other biological activities such as antioxidant and antibacterial properties.

Key words: Halogen bond, Coumarins/quinolinones, 2-bromopropionitrile derivatives, cross-coupling reaction

引用此文

温吉林, 郭鹏, 蒲国良, 满雪玉, 贺春阳. 卤键促进的2-溴丙腈衍生物与香豆素/喹啉酮的交叉偶联反应：合成与转化[J]. 有机化学, doi: 10.6023/cjoc202504009.

Wen, Jilin, Guo, Peng, Pu, Guoliang, Man, Xueyu, He Chun-Yang. Halogen-Bond-Promoted Direct Cross-Coupling of 2-Bromopropionitrile derivatives with Coumarins/Quinolinones: Synthesis and Transformation[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202504009.

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卤键促进的2-溴丙腈衍生物与香豆素/喹啉酮的交叉偶联反应：合成与转化

Halogen-Bond-Promoted Direct Cross-Coupling of 2-Bromopropionitrile derivatives with Coumarins/Quinolinones: Synthesis and Transformation

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