Development of Aromatic Foldamer Building Blocks Bearing Multiple Biogenic Side Chains

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Supramolecular Chemistry

Background:

• Aromatic oligoamides possess inherent rigidity and defined structures, showing promise in medical applications.
• Naturally occurring antibiotics feature similar structures, highlighting their potential for protein and B-DNA binding.
• Current research aims to improve molecular recognition capabilities for drug discovery.

Purpose of the Study:

• To develop a synthetic strategy for quinoline amino acid monomers with diverse side chains.
• To enhance side chain density on helical foldamers for improved protein surface recognition.
• To mimic the dense side chain presentation of alpha-peptides.

Main Methods:

• Synthesized quinoline amino acid monomers with varied side chains at positions 4, 5, and 6.
• Utilized cross-coupling reactions for efficient side chain functionalization.
• Optimized the process for automated solid-phase synthesis.

Main Results:

• Successfully produced a 20-unit aromatic oligoamide foldamer with high purity.
• Demonstrated the incorporation of diverse cationic, anionic, polar, and hydrophobic side chains.
• Validated the potential for molecular recognition applications.

Conclusions:

• The novel synthetic approach advances the construction of aromatic oligoamide foldamers.
• The developed foldamers offer a robust platform for drug discovery and therapeutic applications.
• This methodology enables precise control over side chain presentation for targeted molecular interactions.