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Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Formal synthesis of (-)-kendomycin featuring a Prins-cyclization to construct the macrocycle
Kevin B Bahnck1, Scott D Rychnovsky
1Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
Journal of the American Chemical Society
|September 5, 2008
Summary
Researchers achieved a formal total synthesis of kendomycin using a convergent strategy. An intramolecular Prins cyclization efficiently assembled the macrocyclic core, demonstrating a viable synthetic route.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Kendomycin is a complex natural product with significant biological activity.
- Previous synthetic efforts have faced challenges in constructing its intricate macrocyclic structure.
Purpose of the Study:
- To develop a novel and efficient synthetic strategy for the kendomycin skeleton.
- To demonstrate the utility of an intramolecular Prins cyclization in macrocycle formation.
Main Methods:
- A highly convergent synthetic approach was employed.
- Key fragments, including a benzofuran moiety and an acyclic iodide, were prepared.
- Suzuki coupling was utilized to join the fragments.
- An intramolecular Prins cyclization was the key step for macrocycle assembly.
Main Results:
- The synthesis successfully constructed the kendomycin skeleton.
- The intramolecular Prins cyclization proceeded in good yield.
- Modeling studies supported the feasibility of macrocycle formation.
- The synthesized product was correlated with an advanced intermediate for a formal total synthesis.
Conclusions:
- The developed strategy provides an effective route to the kendomycin core.
- The intramolecular Prins cyclization is a powerful tool for constructing complex macrocycles.
- This work contributes to the broader field of natural product synthesis.
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