Facile access to versatile aza-macrolides through iridium-catalysed cascade allyl-amination/macrolactonization

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Benzo-fused aza-macrolides are important structural motifs in various biologically active compounds.
• Efficient synthetic routes to these macrocycles are crucial for drug discovery and development.

Purpose of the Study:

• To develop a novel and efficient method for the direct synthesis of benzo-fused aza-macrolides.
• To explore the utility of iridium catalysis in constructing complex macrocyclic frameworks.

Main Methods:

• Iridium-catalyzed intermolecular decarboxylative coupling reaction.
• Utilized vinylethylene carbonates and isatoic anhydrides as key starting materials.
• Reaction conditions were optimized for mildness and efficiency.

Main Results:

• Successful direct access to benzo-fused aza-macrolides was achieved.
• The reaction proceeds via a sequential allyl-amination/macrolactonization pathway with CO2 extrusion.
• The synthesized macrocyclic products exhibited favorable fluorescence properties.

Conclusions:

• The developed iridium-catalyzed decarboxylative coupling offers a mild and efficient route to valuable benzo-fused aza-macrolides.
• This methodology provides a new tool for accessing complex macrocyclic structures with potential applications in materials science and medicinal chemistry.