Citation: Wen-Rui Li, Ru-Bing Wang, Huiqiang Wang, Jin-Yao Yong, Yu-Huan Li, Shi-Shan Yu, Shuang-Gang Ma. Ring-reorganization strategy for asymmetric synthesis of sesquiterpenoid illihenin A and its antiviral activity evaluation[J]. Chinese Chemical Letters, ;2025, 36(11): 110945. doi: 10.1016/j.cclet.2025.110945 shu

Ring-reorganization strategy for asymmetric synthesis of sesquiterpenoid illihenin A and its antiviral activity evaluation

Wen-Rui Li ^{a, 1} ,
Ru-Bing Wang ^{a, 1} ,
Huiqiang Wang ^{b, 1} ,
Jin-Yao Yong ^a ,
Yu-Huan Li ^b ,
Shi-Shan Yu ^{a, *,} ,
Shuang-Gang Ma ^{a, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

yushishan@imm.ac.cn

mashuanggang@imm.ac.cn

Received Date: 28 October 2024
Revised Date: 1 February 2025
Accepted Date: 11 February 2025
Available Online: 13 February 2025

Figures(8)

Herein, we report the first asymmetric synthesis of illihenin A, an antiviral sesquiterpenoid bearing a cage-like tricyclo[6.2.2.0^1,5]dodecane skeleton. Starting from an abundant feedstock (-)-α-cedrene, this 19-step synthesis approach features a novel ring-reorganization strategy that includes early stage C7-hydroxylation of the cedrane skeleton and a later-stage ring disassembly-reassembly procedure, affording the desired product with high synthetic efficiency and minimal chiral manipulation. The key transformations include the following: (ⅰ) a hydroxy group-directed SmI₂-mediated reductive coupling to construct the congested tertiary 7-OH cedrane, (ⅱ) a β-fragmentation triggered by an alkoxy radical to release a spiro[4.5]decane, and (ⅲ) an intramolecular Aldol reaction, concomitant with α-epimerization, to furnish the tricyclic framework. In addition, preliminary investigation of antiviral activity against CVB3 revealed that illihenin A can significantly inhibit ROS production and apoptosis.
- Sesquiterpenoid,
- Illihenin A,
- Ring-reorganization,
- Asymmetric synthesis,
- Antiviral activity
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