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Filipin III: Configuration Assignment and Confirmation by Synthetic Correlation
Timothy I. Richardson1, Scott D. Rychnovsky
1Department of Chemistry, University of California, Irvine, California 92717-2025, and University of Minnesota, Minneapolis, Minnesota 55455-0431.
The Journal of Organic Chemistry
|June 26, 1996
Summary
The stereochemical configuration of filipin III was determined using carbon-13 acetonide analysis. This study confirms its structure through synthesis and degradation, revealing unusual molecular conformations.
Area of Science:
- Organic Chemistry
- Structural Biology
- Computational Chemistry
Background:
- Filipin III is a polyene macrolide antibiotic with significant biological activity.
- Determining the precise stereochemical configuration of complex natural products is crucial for understanding their function.
- Previous structural studies of filipin III have been incomplete regarding its stereochemistry.
Purpose of the Study:
- To elucidate the complete stereochemical configuration of filipin III.
- To confirm the structure of filipin III through synthetic and degradative approaches.
- To investigate the conformational preferences of filipin III derivatives using molecular modeling.
Main Methods:
- Stereochemical determination using Carbon-13 (13C) acetonide analysis.
- Synthesis of filipin III derivatives and degradation products.
- Structural confirmation via correlation of synthetic and degradation products.
- Molecular modeling to analyze conformational preferences.
Main Results:
- The relative configurations of nine stereogenic centers in filipin III were identified using three acetonide derivatives.
- The structure was confirmed by synthesis and direct correlation of degradation products (C26-C28 and C1-C16).
- Filipin tetraacetonide and triacetonide derivatives exhibited an unusual anti acetonide in a chair conformation.
Conclusions:
- The stereochemical configuration of filipin III has been definitively determined.
- The study confirms the proposed structure of filipin III through rigorous synthetic and analytical methods.
- Molecular modeling accurately predicted the unusual chair conformation adopted by filipin III acetonide derivatives, challenging previous assumptions about conformational stability.