自由基介导的6-氮杂尿嘧啶官能团化研究进展

doi:10.6023/cjoc202510017

综述与进展

自由基介导的6-氮杂尿嘧啶官能团化研究进展

郑婧斐^a, 吕琪妍^*,ab, 孙凯^a, 陈晓岚^a, 屈凌波^ac, 王金泉^*,d, 於兵^*,a

(^a郑州大学化学学院郑州 450001)
(^b南京林业大学林木生物质低碳高效利用国家工程研究中心南京 210037)
(^c河南省科学院化学研究所郑州 450002)
(^d新加坡发展研究局化学能源与环境可持续发展研究所新加坡 627833)

收稿日期:2025-10-23 修回日期:2025-12-05
基金资助:
国家自然科学基金（22071222、22171249）、111计划（D20003）、河南省自然科学基金（242301420006、252300421245、242300420526）、中原科技创新青年拔尖人才项目

Recent Advances in Functionalization of 6-Azauracils via Radical Reactions

Jing-Fei Zheng^a, Qi-Yan Lv^*,a,b, Kai Sun^a, Xiao-Lan Chen^a, Ling-Bo Qu^{a, c}, Jin-Quan Wang^*,d, Bing Yu^*,a

(^aCollege of Chemistry, Zhengzhou University, Zhengzhou 450001, China.)
(^bNational Engineering Research Center of Low-Carbon Processing and Utilization of Forest Biomass, Nanjing Forestry University, Nanjing 210037, China.)
(^cInstitute of Chemistry, Henan Academy of Sciences, Zhengzhou 450002, China)
(^dInstitute of Sustainability for Chemicals Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, Jurong Island, 627833, Singapore)

Received:2025-10-23 Revised:2025-12-05
Contact: ^*E-mail: qiyanlv@zzu.edu.cn; wang_jinquan@a-star.edu.sg; bingyu@zzu.edu.cn
Supported by:
We acknowledge the financial support from the National Natural Science Foundation of China (22071222, 22171249), the 111 Project (D20003), Natural Science Foundation of Henan Province (242301420006, 252300421245, 242300420526), and Zhongyuan Leading Young Talents in Scientific and Technological Innovation

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摘要/Abstract

6-氮杂尿嘧啶作为尿嘧啶的关键类似物,其骨架是多种生物活性分子的核心结构单元,因此发展其结构修饰新方法具有重要意义。近年来,随着光催化、电催化等绿色、温和的自由基新策略日益成熟,6-氮杂尿嘧啶的自由基官能团化研究已取得重要进展。本文聚焦于2021年以来6-氮杂尿嘧啶通过自由基反应实现的烷基化、芳基化、酰基化、硅基化及三氟甲基化等研究进展,重点综述其新反应方法的设计与机理创新。

关键词: 6-氮杂尿嘧啶, 自由基反应, 光催化, 电催化

6-Azauracil, as a key analog of uracil, serves as a core structural motif in a variety of biologically active molecules. Therefore, the development of novel methods for its structural modification is of significant importance. In recent years, with the maturation of green and mild radical-based strategies, particularly photocatalysis and electrocatalysis, the radical functionalization of 6-azauracils has achieved notable progress. This review focuses on research advances since 2021 concerning the radical-mediated alkylation, arylation, acylation, silylation, and trifluoromethylation of 6-azauracils, with an emphasis on the design and mechanistic innovations of these new reaction methodologies.

Key words: 6-azauracils, radical reaction, photocatalysis, electrocatalysis

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郑婧斐, 吕琪妍, 孙凯, 陈晓岚, 屈凌波, 王金泉, 於兵. 自由基介导的6-氮杂尿嘧啶官能团化研究进展[J]. 有机化学, doi: 10.6023/cjoc202510017.

Jing-Fei Zheng, Qi-Yan Lv, Kai Sun, Xiao-Lan Chen, Ling-Bo Qu, Jin-Quan Wang, Bing Yu. Recent Advances in Functionalization of 6-Azauracils via Radical Reactions[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202510017.

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参考文献

[1] a) Z. Rankovic, J. Cai, X. Fradera, M. Dempster, A. Mistry, A. Mitchell, C. Long, E. Hamilton, A. King, S. Boucharens, C. Jamieson, J. Gillespie, I. Cumming, J. Uitdehaag, M. v. Zeeland, Bioorg. Med. Chem. Lett. 2010, 20, 1488-1490; b) N. Hin, B. Duvall, D. Ferraris, J. Alt, A. G. Thomas, R. Rais, C. Rojas, Y. Wu, K. M. Wozniak, B. S. Slusher, T. Tsukamoto,J. Med. Chem. 2015, 58, 7258-7272; c) A. Schön, E. Kaminska, F. Schelter, E. Ponkkonen, E. Korytiaková, S. Schiffers, T. Carell, Angew. Chem. Int. Ed. 2020, 59, 5591-5594.
[2] Y. Xia, Y. Li, Q. Xiao, Z. Cai, Q. Yang, Y. Hu, Z. Mei, G. Bao, H. Yuan, Food Chem. 2024, 453, 139652.
[3] H. L. Maslen, D. Hughes, M. Hursthouse, E. De Clercq, J. Balzarini, C. Simons, J. Med. Chem. 2004, 47, 5482-5491.
[4] T. A. Shaw, C. J. Ablenas, G. F. Desrochers, M. H. Powdrill, D. A. Bilodeau, J.-F. Vincent-Rocan, M. Niu, A. Monette, A. J. Mouland, A. M. Beauchemin, J. P. Pezacki,Bioconjugate Chem. 2020, 31, 1537-1544.
[5] a) J. Pontillo, Z. Guo, D. Wu, R. S. Struthers, C. Chen, Bioorg. Med. Chem. Lett. 2005, 15, 4363-4366; b) P. J. Dudfield, V.-D. Le, S. D. Lindell, C. W. Rees,Journal of the Chemical Society, Perkin Transactions 1999, 2929-2936.
[6] P. Ghosh, N. Y. Kwon, S. Kim, S. Han, S. H. Lee, W. An, N. K. Mishra, S. B. Han, I. S. Kim, Angew. Chem. Int. Ed. 2021, 60, 191-196.
[7] Z. Cai, Y. Han, Y. Zhang, H. Zhang, J. Zhao, S. Yang, Green Chem. 2023, 25, 5721-5726.
[8] a) J. Fang, R. Tian, J. Chen, X. Liu,Chin. J. Org. Chem. 2025, 45, 22-41; b) Y. Wang, R. Li, J. Huang, F. Jia, Z. Wang, W. Wei, Z. Yang, D. Yi, Chem. Commun. 2025, 61, 17137-17140.
[9] a) D. S. Finis, D. A. Nicewicz,J. Am. Chem. Soc. 2024, 146, 16830-16837; b) J. Großkopf, C. Gopatta, R. T. Martin, A. Haseloer, D. W. C. MacMillan, Nature 2025, 641, 112-121; c) S. Sarkar, K. P. S. Cheung, V. Gevorgyan, Chem. Sci. 2020, 11, 12974-12993; d) C. Niu, J. Yang, K. Yan, Z. Su, B. Li, J. Wen, J. Org. Chem. 2024, 89, 13284-13295.
[10] a) L. L. Schafer, C. H. M. Zheng, Synthesis 2024, 57, 522-538; b) C. Niu, J. Yang, K. Yan, J. Xie, W. Jiang, B. Li, J. Wen, iScience 2022, 25, 104253; c) Y. Wang, J. Wang, C. Chen, L. Song, Z. Wang, W. Wei, D. Yi, Chem. Commun. 2025, 61, 10812-10815; d) C. Zhang, F. Liu, Y. Zhang, C. Song, Eur. J. Med. Chem. 2024, 268, 116234; e) C. Xin, W. He, Chin. J. Org. Chem. 2024, 44,3790-3792; f) Q.-W. Gui, B.-B. Wang, S. Zhu, F.-L. Li, M.-X. Zhu, M. Yi, J.-L. Yu, Z.-L. Wu, W.-M. He,Green Chem. 2021, 23, 4430-4434; g) Y. Wu, J. Chen, J. Ning, X. Jiang, J. Deng, Y. Deng, R. Xu, W. He, Green Chem. 2021, 23, 3950-3954; h) J. Hou, J. Jiang, H. Dai, J. Wang, T. Li, X. Chen, W. He, Sci. China Chem. 2025, 68, 1945-1951; i) Y. Wen, J.-C. Hou, Q. Zhou, S. Wang, J. Jiang, Z. Yang, H.-T. Zhu, Z. Wang, W. He, Chin. Chem. Lett. 2025, 36, 111795.
[11] K. C. Gulipalli, S. Bodige, P. Ravula, R. S. Bolla, S. Endoori, Rao Cherukumalli, P. Koteswara, N. Seelam,Asian J. Org. Chem. 2018, 30, 2495-2501.
[12] H. Zhang, J. Chen, C. Lu, Y. Han, Y. Zhang, J. Zhao, J. Org. Chem. 2021, 86, 11723-11735.
[13] a) Y. Wu, Z. Liu, Y. Li, J. Chen, X. Zhu, P. Na,Chin. J. Catal. 2019, 40, 60-69; b) D. Liu, S. Chen, Y. Zhang, R. Li, T. Peng, Appl. Catal. B Environ. Energy 2023, 333, 122805; c) Y. Wei, M. Z. Shahid, S. Lyu, W. Sun, S. Lyu, RSC Adv. 2021, 11, 22618-22624; d) H. Hu, Y. Zhang, K. A. Robinson, Y. Yue, R. Nie, Appl. Catal. B Environ. Energy 2022, 316, 121595; e) J. Hou, W. Cai, H. Ji, L. Ou, W. He, Chin. Chem. Lett. 2025, 36, 110469.
[14] P. Ghosh, N. Y. Kwon, Y. Byun, N. K. Mishra, J. S. Park, I. S. Kim, ACS Catal. 2022, 12, 15707-15714.
[15] Y. Tan, W. Xuekun, Y. Han, Y. Zhang, H. Zhang, J. Zhao, J. Org. Chem. 2022, 87, 8551-8561.
[16] F. Cheng, L. Fan, Q. Lv, X. Chen, B. Yu, Green Chem. 2023, 25, 7971-7977.
[17] a) C. Niu, J. Yang, K. Yan, Z. Su, B. Li, J. Wen, J. Org. Chem. 2024, 13284-13295; b) H. Ji, K. Wang, W. Ouyang, Q. Luo, H. Li, W. He, Green Chem. 2023, 25,7983-7987; c) W. Ouyang, J. Jiang, Y. Jiang, T. Li, Y. Liu, H. Ji, L. Ou, W. He,Chin. Chem. Lett. 2024, 35, 110038.
[18] a) T. Yan, J. Yang, K. Yan, Z. Wang, B. Li, J. Wen,Angew. Chem. Int. Ed. 2024, 63, e202405186; b) L. Tan, W. Li, S. Tu, X. Zhong, X. Li, X. Du, Z. Zhang, S. Wei, D. Yi, Chin. J. Chem. 2025, 43, 2533-2538.
[19] S. P. Panda, S. K. Hota, R. Dash, L. Roy, S. Murarka, Org. Lett. 2023, 25, 3739-3744.
[20] a) J. Kanazawa, K. Maeda, M. Uchiyama,J. Am. Chem. Soc. 2017, 139, 17791-17794; b) B. R. Shire, E. A. Anderson, JACS Au 2023, 3, 1539-1553.
[21] J. Zhu, Y. Guo, Y. Zhang, W. Li, P. Zhang, J. Xu, Green Chem. 2023, 25, 986-992.
[22] Z. Cai, X. Cao, H. Zhang, Y. Zhang, J. Zhao, Org. Chem. Front. 2024, 11, 5516-5523.
[23] a) L. F. T. Novaes, J. Liu, Y. Shen, L. Lu, J. M. Meinhardt, S. Lin, Chem. Soc. Rev. 2021, 50, 7941-8002; b) Y. Wen, J. Hou, Q. Zhou, S. Wang, J. Jiang, Z. Yang, H. Zhu, Z. Wang, W. He,Chin. Chem. Lett. 2025, 36, 111795; c) X. Sun, J. Yang, K. Yan, X. Zhuang, J. Yu, X. Song, F. Zhang, B. Li, J. Wen, Chem. Commun. 2022, 58, 8238-8241; d) B. Li, H. Qin, K. Yan, J. Ma, J. Yang, J. Wen, Org. Chem. Front. 2022, 9, 6861-6868.
[24] a) P. Niu, J. Yang, Y. Yuan, Y. Zhang, C. Zhou, X. Bao, C. Huo, Green Chem. 2021, 23, 774-779; b) B. Li, H. Qin, K. Yan, J. Ma, J. Yang, J. Wen, Org. Chem. Front. 2022, 9, 6861-6868; c) P. Xiang, B. Yu, Chin. J. Org. Chem. 2024, 44, 2057-2058.
[25] B. Jat, D. K. Yadav, S. S. Badsara, S. Sharma, Org. Biomol. Chem. 2025, 23, 4846-4854.
[26] R. Dash, S. P. Panda, K. S. Bhati, S. Sharma, S. Murarka, Org. Lett. 2024, 26, 7227-7232.
[27] X. Tang, X. Jia, Z. Huang, J. Am. Chem. Soc. 2018, 140, 4157-4163.
[28] B. Maity, S. Dutta, L. Cavallo, Chem. Soc. Rev. 2023, 52, 522-545.
[29] L. Qiao, W. Yang, X. Zhao, E. Li, X. Chen, L. Qu, B. Yu, Org. Chem. Front. 2024, 11, 5791-5797.
[30] C. Xiang, S. Yu, H. Fei, C. Pan, J. Yu, Eur. J. Org. Chem. 2024, 27, e202400245.
[31] X. Huang, D. Zhang, Q. Li, Z. Xie, Z. Le, Z. Zhu, Org. Lett. 2024, 26, 3727-3732.
[32] R. Das, N. Sakander, S. Kundu, D. Mukherjee, T. Kundu, Org. Lett. 2025, 27, 5491-5496.
[33] a) R. Ci, J. Qiao, Q. Gan, B. Chen, C. Tung, L.-Z. Wu, Green Chem. 2023, 25, 8500-8504; b) J. Yao, Y. Xiao, H. Li, X. Yang, J. Du, Y. Yin, L. Feng, W. Duan, L. Yu, Org. Lett. 2024, 26, 7307-7312; c) J. Xu, R. Li, Y. Ma, J. Zhu, C. Shen, H. Jiang, Nat. Commun. 2024, 15, 6791; d) L. Liu, M. Liu, J. Yang, B. Zhu, X. Wang, Curr. Org. Chem. 2018, 22, 2023-2028.
[34] K. Sun, A. Shi, Y. Liu, X. Chen, P. Xiang, X. Wang, L. Qu, B. Yu, Chem. Sci. 2022, 13, 5659-5666.
[35] P. Meher, S. P. Panda, S. K. Mahapatra, K. R. Thombare, L. Roy, S. Murarka, Org. Lett. 2023, 25, 8290-8295.
[36] Y. Pan, Y. Zhu, S. Li, G. Li, Z. Ma, Y. Qian, W. Huang, Chem. Commun. 2024, 60, 3665-3668.
[37] a) G. S. Lee, S. H. Hong,Acc. Chem. Res. 2023, 56, 2170-2184; b) T. Hao, Y. Wei, M. Shi, Green Synth. Catal. 2025.
[38] Y. Sha, Y. Zhang, Q. Tian, H. Tong, W. Zhang, X. Zhu, Z. Sun, W. Chu, Adv. Synth. Catal. 2024, 366, 3166-3172.
[39] Z. Zhang, F. Cheng, X. Ma, K. Sun, X. Huang, J. An, M. Peng, X. Chen, B. Yu, Green Chem. 2024, 26, 7331-7336.
[40] a) S. Bacaicoa García, M. Martos González, W. Y. Graf, A. Runemark, G. H. Shinde, G. G. G. Ghotekar, H. Sundén, Green Chem. 2025, 27, 8112-8119; b) Q. Li, P. Dai, H. Tang, M. Zhang, J. Wu,Chem. Sci. 2022, 13, 9361-9365; c) J. Huang, R. Li, Y. Lv, F. Jia, H. Yue, Z. Yang, Z. Wang, W. Wei, D. Yi, J. Org. Chem. 2025, 90, 14805-14813.
[41] a) N. Bai, X. Wang, Z. Wang, F. Liu, Z.-Q. Rong, Org. Chem. Front. 2022, 9, 5942-5948; b) F. Zeng, H. Zhu, R. Wang, X. Yuan, K. Sun, L. Qu, X. Chen, B. Yu,Chin. J. Catal. 2023, 46, 157-166.
[42] C. Pan, D. Chen, M. Zeng, H. Tian, J. Yu, Eur. J. Org. Chem. 2024, 27, e202301177.
[43] C. B. Kelly, M. A. Mercadante, N. E. Leadbeater, Chem. Commun. 2013, 49, 11133-11148.
[44] J. An, X. Chen, Y. Zhuang, P. Xiang, K. Sun, X. Chen, P. Liu, L. Qu, B. Yu, J. Org. Chem. 2025, 90, 11486-11500.
[45] G. A. Showell, J. S. Mills, Drug Discovery Today 2003, 8, 551-556.
[46] Y. Yu, M. You, J. Yu, W. Kong, C. Zhang, J. Bai, W. Li, T. Li, Adv. Synth. Catal. 2024, 367, e202400857.
[47] H. Cui, X. Qiao, T. Shi, W. Wei, H. Yue, Z. Wang, Z. Ma, Z. Yang, Chem. Commun. 2025, 61, 17890-17893.
[48] a) H. Xiao, Z. Zhang, Y. Fang, L. Zhu, C. Li, Chem. Soc. Rev. 2021, 50, 6308-6319; b) C. Ge, L. Qiao, Y. Zhang, K. Sun, J. An, M. Peng, X. Chen, L. Qu, B. Yu,Chin. J. Chem. 2024, 42, 1679-1685; c) C. Liu, Z. Zhang, Z. Zhao, J. Jiang, Z. Yang, Z. Wang, W. He, J. Org. Chem. 2025, 90, 11982-11989; d) S. Liu, K. Chen, D. Sun, Q. Liu, X. Chen, Chin. J. Org. Chem. 2025, 45, 2545-2551; e) Q. Peng, J. Jiang, Z. Liao, Z. Wu, L. Ou, H. Dai, J. Peng, W. He, ACS Sustainable Chem. Eng. 2025, 13, 10971-10977; f) Q. Peng, N. Li, J. Hou, C. He, Y. Yang, C. Zhuang, L. Ou, M. Yuan, W. He, Chin. Chem. Lett. 2025, 36, 111402.
[49] N. Deng, Y. Wu, Y. Feng, W. Hsieh, J. Song, Y. Lin, Y. Tseng, W. Liao, Y. Chu, Y. Liu, E. Chang, C. Liu, S. Sheu, M. Su, H. Kuo, S. N. Cohen, T.-H. Cheng,Proc. Natl. Acad. Sci. USA 2022, 119, e2204779119.
[50] K. K. Das, A. Hajra, RSC Adv. 2025, 15, 11370-11376.