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2026 202605025

DOI: https://doi.org/10.6023/cjoc202605025

研究论文

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 ,
  • 蒲雁林 ,
  • 包文 ,
  • 朱道勇 ,
  • 官瑞丽 ,
  • 张野 ,
  • 王少华
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  • 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

  网络出版日期: 2026-09-08

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.

收起

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

  • Gu-Han Qin ,
  • Yan-Lin Pu ,
  • Wen Bao ,
  • Dao-Yong Zhu ,
  • Ruili Guan ,
  • Ye Zhang ,
  • Shao-Hua Wang
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  • 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
†These authors contributed equally to this work.

Received date: 2026-05-25

  Revised date: 2026-07-23

  Online published: 2026-09-08

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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摘要

松香烷型三环二萜具有独特的6/6/6稠合三环骨架, 广泛表现出多样的药理活性, 在药物研发中占据重要地位. 近年来, 活性次甲基腈类化合物因其作为合成砌块在天然产物全合成与药物分子设计中的核心价值, 以及氰基官能团转化的高效性和灵活性, 持续受到合成化学界的关注. 基于此, 本文发展了一种以活性次甲基腈类化合物为引发剂的多烯环化策略, 用于高效构建6/6/6稠合三环体系. 该方法利用Cu(OTf)2催化, 经DTBP氧化介导的自由基途径产生高活性中间体, 成功实现从简单开链多烯腈类前体向复杂多环骨架的快捷转化, 充分展现了其在构筑松香烷型天然产物核心结构中的合成潜力. 该反应条件温和, 底物适用范围广, 官能团耐受性良好, 并具有优异的非对映选择性, 为相关天然产物及药物分子的合成提供了新思路.

关键词： 多烯环化; 活性次甲基腈; 自由基; 6/6/6稠合三环

本文引用格式

秦谷涵 , 蒲雁林 , 包文 , 朱道勇 , 官瑞丽 , 张野 , 王少华 . 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[J]. 有机化学, 2026 : 202605025 . DOI: 10.6023/cjoc202605025

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

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