Activated Methine Nitriles-Initiated Radical Polyene Cyclization for the Synthesis of Abietane-Type Tricyclic Diterpenoid Skeletons

doi:10.6023/cjoc202605025

Chinese Journal of Organic Chemistry Previous Articles

ARTICLE

基于活性次甲基腈的自由基多烯环化: 松香烷型三环二萜骨架的构筑新方法

秦谷涵^a,†, 蒲雁林^a,†, 包文^a, 朱道勇^a, 官瑞丽^b,*, 张野^a,*, 王少华^a,*

^a兰州大学药学院&天然产物化学全国重点实验室兰州 730000;
^b空军军医大学&特殊作业环境危害评估与防治教育部重点实验室西安 710032

收稿日期:2026-05-25 修回日期:2026-07-23
基金资助:
国家重点研发计划(No. 2023YFA1506404), 国家自然科学基金(22401123, 22501118), 甘肃省科技计划(23ZDFA003, 23ZDFA015, 23JRRA1028, 23CXGA0043, 24JRRA941, 24ZDFA003, 24ZD13FA017, 26JRRA175), 兰州市科技计划(2023-QN-18, 2023-1-17, 2024-1-17), 中央高校基本科研业务专项(lzujbky-2024-17, 2025CXZX-106, LZU-GXJJ-2025-007), 国家卫生健康委中心临床科研专项(WKZX2023CX200002)资助项目.

Activated Methine Nitriles-Initiated Radical Polyene Cyclization for the Synthesis of Abietane-Type Tricyclic Diterpenoid Skeletons

Gu-Han Qin^a,†, Yan-Lin Pu^a,†, Wen Bao^a, Dao-Yong Zhu^a, Ruili Guan^b,*, Ye Zhang^a,*, Shao-Hua Wang^a,*

^aSchool of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou, 730000;
^bMinistry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Fourth Military Medical University, Xi’an, 710032

Received:2026-05-25 Revised:2026-07-23
Contact: *E-mail: wangshh@lzu.edu.cn; zhang_ye@lzu.edu.cn; 772036128@qq.com
About author:^†These authors contributed equally to this work.
Supported by:
National Key R&D Program of China (2023YFA1506404), the National Natural Science Foundation of China (22401123, 22501118), the Science and Technology Program of Gansu Province (23ZDFA003, 23ZDFA015, 23JRRA1028, 23CXGA0043, 24JRRA941, 24ZDFA003, 24ZD13FA017, 26JRRA175), the Lanzhou Science and Technology Planning Project (2023-QN-18, 2023-1-17, 2024-1-17), the Fundamental Research Funds for the Central Universities (lzujbky-2024-17, 2025CXZX-106, LZU-GXJJ-2025-007), the DCMST.NHC Clinical Research Project (WKZX2023CX200002).

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Abstract

Abietane-type tricyclic diterpenes, featuring a fused 6/6/6 ring system, exhibit diverse pharmacological activities and are of significant importance in drug discovery. Active methine nitriles have recently attracted considerable interest as versatile building blocks in total synthesis and medicinal chemistry due to their facile cyano-group transformations. Herein, we report a Cu(OTf)₂-catalyzed polyene cyclization strategy initiated by active methine nitriles for the efficient construction of the 6/6/6 tricyclic framework. This transformation proceeds through a DTBP-mediated radical oxidation pathway, generating highly reactive intermediates that enable rapid conversion of simple acyclic polyene nitriles into complex polycyclic architectures. The method features mild conditions, broad substrate scope, good functional group tolerance, and excellent diastereoselectivity, thus offering a powerful approach to the core skeleton of abietane-type natural products and related pharmacologically relevant molecules.

Key words: polyene cyclization, active methine nitriles, radical process, 6/6/6 fused tricyclic frameworks

Cite this article

Gu-Han Qin, Yan-Lin Pu, Wen Bao, Dao-Yong Zhu, Ruili Guan, Ye Zhang, Shao-Hua Wang. Activated Methine Nitriles-Initiated Radical Polyene Cyclization for the Synthesis of Abietane-Type Tricyclic Diterpenoid Skeletons[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202605025.

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基于活性次甲基腈的自由基多烯环化: 松香烷型三环二萜骨架的构筑新方法

Activated Methine Nitriles-Initiated Radical Polyene Cyclization for the Synthesis of Abietane-Type Tricyclic Diterpenoid Skeletons

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