Total Synthesis of 4-epi-Bengamide E

Area of Science:

• Marine Natural Products Chemistry
• Organic Synthesis
• Medicinal Chemistry

Background:

• Bengamide E, a marine natural product isolated from Jaspidae sponges, exhibits significant antitumor, antibiotic, and anthelmintic properties.
• Several total syntheses of Bengamide E and its analogues have been reported to understand structure-activity relationships.
• The stereoisomer 4-epi-Bengamide E has not been synthesized previously, limiting investigations into its specific biological contributions.

Purpose of the Study:

• To report the first total synthesis of 4-epi-Bengamide E.
• To explore novel synthetic strategies for accessing stereoisomers of complex natural products.
• To provide a foundation for further studies on the biological activities of Bengamide E analogues.

Main Methods:

• Chemoenzymatic desymmetrization of biobased starting materials.
• Diastereoselective Passerini reaction utilizing a chiral aldehyde.
• Employing a novel lysine-derived isocyanide in the Passerini reaction.

Main Results:

• Successful synthesis of 4-epi-Bengamide E, the first reported synthesis of this stereoisomer.
• Demonstration of a chemoenzymatic approach for generating enantiomerically pure building blocks.
• Validation of a diastereoselective Passerini reaction for constructing the core structure.

Conclusions:

• The developed synthetic route provides access to 4-epi-Bengamide E, enabling future biological evaluations.
• This work highlights the utility of chemoenzymatic methods and Passerini reactions in complex molecule synthesis.
• The synthesis opens new avenues for exploring the medicinal chemistry of Bengamide E derivatives.