Citation: Jiulong Li, Pengxin Ren, Lin Wang, Yuting Zhang, Peng Yang, Weiwei He, Ang Li. Inverse-electron-demand Diels–Alder approach to densely substituted bicyclo[3.2.2]nonanes: Discovery of an autophagy regulator[J]. Chinese Chemical Letters, ;2026, 37(5): 111381. doi: 10.1016/j.cclet.2025.111381 shu

Inverse-electron-demand Diels–Alder approach to densely substituted bicyclo[3.2.2]nonanes: Discovery of an autophagy regulator

Jiulong Li ^{a, b} ,
Pengxin Ren ^{a, b} ,
Lin Wang ^c ,
Yuting Zhang ^c ,
Peng Yang ^{a, *,} ,
Weiwei He ^{c, *,} ,
Ang Li ^{b, *,}

a.
College of Chemistry & Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China
b.
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China
c.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

yangpeng_imb@zzu.edu.cn

heweiwei@ecust.edu.cn

ali@sioc.ac.cn

Received Date: 24 March 2025
Revised Date: 22 May 2025
Accepted Date: 26 May 2025
Available Online: 27 May 2025

Figures(4)

Natural products bearing a bicyclo[3.2.2]nonane motif pose a considerable challenge to chemical synthesis. We developed a europium-promoted inverse-electron-demand Diels–Alder reaction of benzo[2,3]tropone derivatives with electron-rich olefins, which offers an expeditious approach to densely substituted bicyclo[3.2.2]nonanes. This method enabled the concise synthesis of a tetracyclic amine, subsequently identified as a downstream suppressor of autophagy.
- Bicyclo[3.2.2]nonane,
- Benzo[2,3]tropone,
- Inverse-electron-demand Diels–Alder reaction,
- Autophagy regulation
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