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Stereoselective synthesis and the polyene macrolide antibiotics
1Department of Chemistry, University of Minnesota, Minneapolis 55455.
Acta Pharmaceutica Nordica
|January 1, 1990
Summary
Chemists have developed a new method to synthesize complex alternating polyol chains, crucial for creating polyene macrolide antibiotics like roflamycoin. This approach utilizes novel 1,3-diol synthons for efficient chain assembly.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Polyene macrolide antibiotics, such as roflamycoin, possess complex stereochemistry.
- The synthesis of alternating polyol chains, a key structural feature, is challenging due to a lack of simple assembly methods.
Purpose of the Study:
- To develop a simple, convergent method for assembling alternating polyol chains.
- To overcome the synthetic challenges posed by the stereochemical complexity of polyene macrolides.
Main Methods:
- Introduction of a new class of 1,3-diol synthons: 6-alkyl-4-thiophenyl-1,3-dioxanes.
- Preparation of synthons from readily available homoallylic alcohols or beta-hydroxyesters.
- Stereoselective reduction of synthons to form configurationally stable alkyllithiums.
- Reaction of alkyllithiums with electrophiles to yield protected syn or anti-1,3-diols.
Main Results:
- A novel and convergent strategy for constructing alternating polyol chains has been established.
- The method allows for the controlled synthesis of both syn and anti 1,3-diols.
- The 1,3-diol synthons are accessible in optically pure forms.
Conclusions:
- The developed method provides an efficient route to synthesize complex polyol chains essential for polyene macrolide antibiotic synthesis.
- This breakthrough simplifies the retrosynthetic analysis and assembly of challenging molecular architectures.