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Ring-closing metathesis approach to dictyostatin
Cyrous O Kangani1, Arndt M Brückner, Dennis P Curran
1Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Organic Letters
|January 28, 2005
Summary
A new esterification and ring-closing metathesis strategy enables efficient synthesis of complex natural products like dictyostatin and discodermolide. This method allows for selective fragment coupling, creating the crucial C10-C11 alkene bond with high Z-selectivity.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Dictyostatin and discodermolide are complex marine natural products with significant biological activities.
- Efficient synthetic routes are crucial for accessing these compounds for further study and potential therapeutic applications.
- Previous synthetic strategies faced challenges in fragment coupling and stereoselectivity.
Purpose of the Study:
- To develop a novel and efficient synthetic approach for dictyostatin and discodermolide.
- To establish a facile method for fragment coupling of key segments of these natural products.
- To achieve high stereoselectivity in the formation of the C10-C11 alkene.
Main Methods:
- The study employed an esterification reaction followed by ring-closing metathesis (RCM).
- Two main fragments of the target natural products were synthesized and coupled.
- The RCM reaction was optimized to control the geometry of the newly formed alkene.
Main Results:
- A convergent synthetic strategy was successfully implemented.
- Facile fragment coupling was achieved at the C10-C11 position.
- High to complete Z-selectivity was observed for the C10-C11 alkene formation.
Conclusions:
- The developed esterification/RCM approach provides an efficient route to dictyostatin and discodermolide.
- This methodology offers a powerful tool for the synthesis of complex polyketides.
- The high Z-selectivity achieved simplifies the synthesis and purification process.