Citation: Hongjin Xu, Jinghua Wu, Hui Wang, Huanfeng Jiang, Zhiqiang Ma. Asymmetric total synthesis of (–)-14-epi-sinugyrosanolide A[J]. Chinese Chemical Letters, ;2026, 37(3): 112018. doi: 10.1016/j.cclet.2025.112018 shu

Asymmetric total synthesis of (–)-14-epi-sinugyrosanolide A

Hongjin Xu ^a ,
Jinghua Wu ^a ,
Hui Wang ^a ,
Huanfeng Jiang ^a ,
Zhiqiang Ma ^{a, b, *,}

a.
Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry & Chemical Engineering, South China University of Technology, Guangzhou 510641, China
b.
State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China

cezqma@scut.edu.cn

Received Date: 9 September 2025
Revised Date: 21 October 2025
Accepted Date: 22 October 2025
Available Online: 22 October 2025

Figures(4)

The α,β-butenolide moiety serves as a valuable electrophile in Michael additions and cycloadditions, enabling the direct and atom-economical construction of γ-butyrolactones—a unique structural motif prevalent in natural products. However, its susceptibility to aromatization limits its applications in complex natural products synthesis. Herein, we report the asymmetric synthesis of (–)-14-epi-sinugyrosanolide A, a stereoisomer of the natural product sinugyrosanolide A, in which the aromatization of α,β-butenolide moiety was inhibited. A mild acid-promoted intramolecular [5 + 2] cycloaddition could rapidly assemble the synthetically challenging 5,5,7,6 core found in several Sinularia diterpenoids. The key cycloaddition precursor was prepared through an unconventional sequence involving an aldol reaction of dihydropyranone acetal derivatives and aldehyde, followed by ring-closing metathesis (RCM). This research not only accomplishes the asymmetric synthesis of (–)-14-epi-sinugyrosanolide A, but also shows its potential for synthesizing other cembranoid and norcembranoid natural products. More importantly, it establishes an alternative approach toward synthesizing structurally complex molecules containing γ-butyrolactone moiety.
- α,β-Butenolide,
- [5+2] cycloaddition,
- Total synthesis,
- Cembranoids and norcembranoids
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