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Published on: June 13, 2022
Total synthesis of (+/-)-aspercyclide A and its C19 methyl ether.
James L Carr1, Daniel A Offermann, Mary D Holdom
1Department of Chemistry, South Kensington campus, Imperial College, London, UK SW7 2AZ.
The total synthesis of aspercyclide A and a related compound was achieved. The study highlights a novel macrocyclisation method to construct the core structure.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Aspercyclide A is a complex natural product with potential biological activity.
- Efficient synthetic routes to complex macrocyclic structures are valuable in medicinal chemistry.
Purpose of the Study:
- To describe the total synthesis of (+/-)-aspercyclide A and its C19 methyl ether.
- To develop and showcase a novel macrocyclisation strategy.
Main Methods:
- Total synthesis utilizing multi-step organic reactions.
- Heck-Mizoroki macrocyclisation to form an 11-membered ring.
- Construction of the (E)-styrenyl biaryl ether lactone core.
Main Results:
- Successful synthesis of (+/-)-aspercyclide A (1).
- Successful synthesis of the C19 methyl ether analogue (15a).
- Demonstration of the Heck-Mizoroki macrocyclisation for forming the core structure.
Conclusions:
- The described synthetic route provides access to aspercyclide A and its analogues.
- The Heck-Mizoroki macrocyclisation is an effective method for constructing the target macrocyclic core.
- This work contributes to the field of natural product synthesis and methodology development.
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