Total syntheses of bengamides B and E

Area of Science:

• Marine natural product chemistry
• Organic synthesis
• Medicinal chemistry

Background:

• Bengamides B and E are cytotoxic marine natural products with potential therapeutic applications.
• Their complex structures present significant challenges for chemical synthesis.

Purpose of the Study:

• To develop efficient and scalable total syntheses of bengamides B and E.
• To explore novel synthetic methodologies for constructing complex polyhydroxylated lactones and substituted aminocaprolactams.

Main Methods:

• Amide coupling of a protected polyhydroxylated lactone intermediate with a substituted aminocaprolactam intermediate.
• Synthesis of the lactone intermediate from alpha-D-glucoheptonic gamma-lactone.
• Synthesis of the lactam intermediate from (5R)-5-hydroxy-L-lysine.
• Key reactions included selective acetonide deprotection, (E)-selective olefination, and Mitsunobu inversion.

Main Results:

• Successful total syntheses of bengamides B and E were accomplished.
• The synthetic route established a protected polyhydroxylated lactone intermediate and a substituted aminocaprolactam intermediate.
• Key stereochemical configurations were controlled using selective reactions.

Conclusions:

• The described synthetic strategies provide access to bengamides B and E.
• The methodologies employed are potentially applicable to the synthesis of other complex marine natural products.
• This work contributes to the field of natural product synthesis and drug discovery.