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Epi-, epoxy-, and C2-modified bengamides: synthesis and biological evaluation
Francisco Sarabia1, Francisca Martín-Gálvez, Cristina García-Ruiz
1Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n 29071-Málaga, Spain. frsarabia@uma.es
The Journal of Organic Chemistry
|May 8, 2013
Summary
Structural modifications to bengamide E analogues did not enhance their antitumor activities. The polyketide chain is crucial for the natural products' anticancer effects, and alterations are not beneficial.
Area of Science:
- Natural Product Synthesis
- Medicinal Chemistry
- Organic Synthesis
Background:
- Bengamides are natural products with demonstrated antitumoral activities.
- Understanding structure-activity relationships is key to developing novel cancer therapeutics.
- Modifications to natural product scaffolds can yield compounds with improved efficacy or reduced toxicity.
Purpose of the Study:
- To investigate the impact of structural and stereochemical modifications of the polyketide chain of bengamide E on its antitumoral activity.
- To synthesize novel bengamide E analogues with variations at C-2 and C-3 positions and the inclusion of oxirane rings.
- To evaluate the necessity of the intact polyketide chain for the observed anticancer properties.
Main Methods:
- Employed a novel asymmetric epoxidation method using chiral sulfonium salts.
- Utilized Miyashita's methodology for oxirane-ring-opening with double inversion.
- Performed aldol reactions as an alternative synthetic route to target analogues.
- Conducted biological evaluations of synthesized bengamide E analogues.
Main Results:
- Successfully synthesized various bengamide E analogues with modified stereochemistry and substituents.
- Demonstrated the utility of a new asymmetric epoxidation and established ring-opening methodologies.
- Biological testing revealed that structural and configurational modifications to the polyketide chain abolish antitumoral activity.
- The polyketide chain was found to be essential for the anticancer effects of bengamides.
Conclusions:
- The polyketide chain of bengamide E is indispensable for its antitumoral activity.
- Structural and stereochemical modifications of this chain do not lead to improved anticancer properties.
- Further research should focus on preserving the integrity of the polyketide scaffold in bengamide-based drug design.
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