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Published on: February 6, 2020
How Intramolecular Epoxide-Opening Cascades Generate Polyether Ionophores, Marine Ladder Polyethers, and
Zhi-Yuan Sun1, Feng-Xing Li1, Xiao-Chi Wang1
1The State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
The Journal of Organic Chemistry
|July 2, 2026
Summary
Researchers investigated polycyclic polyether synthesis using epoxide cyclizations. They discovered distinct mechanisms for forming linked-THF-type and trans-fused-type polyethers, revealing control over cyclization pathways.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Chemical Biology
Background:
- Polycyclic polyethers, including ionophores, marine ladder polyethers, and oxasqualenoids, are important natural products.
- Previous synthetic efforts focused on intramolecular epoxide-opening cyclizations, inspired by proposed biosynthetic pathways.
Purpose of the Study:
- To elucidate the mechanisms of intramolecular tandem epoxide-opening cyclizations in polycyclic polyether synthesis.
- To investigate the formation pathways of linked-THF-type and trans-fused-type polyethers.
- To explore the synthesis of oxasqualenoids using controlled cyclization strategies.
Main Methods:
- Utilized Nuclear Magnetic Resonance (NMR) spectroscopy to monitor reaction pathways.
- Studied the cyclization of polyepoxide precursors.
- Manipulated nucleophilicity of hydroxyl groups to control cyclization outcomes.
Main Results:
- The linked-THF-type polyether glabrescol forms stepwise via hydroxy-to-epoxide ring-opening cyclizations.
- All ether rings in the trans-fused-type polyether hemibrevitoxin B form simultaneously or rapidly.
- Synthesized oxasqualenoid skeletons through combined hydroxy-to-epoxide and epoxide-to-epoxonium cyclizations.
Conclusions:
- The mechanism of polycyclic polyether formation varies significantly between linked-THF-type and trans-fused-type structures.
- Controlling hydroxyl group nucleophilicity allows for selective manipulation of cyclization pathways.
- This study provides insights into the biosynthesis and synthetic strategies for complex polyether natural products.
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