Small peptide diversification through photoredox-catalyzed oxidative C-terminal modification

Area of Science:

• Organic Chemistry
• Peptide Chemistry
• Catalysis

Background:

• Peptide modification is crucial for developing new therapeutics and materials.
• Efficient methods for creating complex peptide structures are in high demand.
• Oxidative decarboxylative coupling offers a promising route for C-C and C-heteroatom bond formation.

Purpose of the Study:

• To develop a novel photoredox-catalyzed oxidative decarboxylative coupling reaction for small peptides.
• To synthesize diverse N,O-acetals as versatile intermediates.
• To explore the utility of these intermediates in constructing novel peptide scaffolds and bioconjugates.

Main Methods:

• Photoredox catalysis was employed to drive the oxidative decarboxylative coupling.
• Small peptides were coupled to generate N,O-acetal intermediates.
• Phenols, indoles, and amino acids with nucleophilic side chains were used as coupling partners.

Main Results:

• A variety of N,O-acetals were successfully synthesized from small peptides.
• These intermediates were effectively used for the addition of phenols and indoles.
• Novel peptide scaffolds and bioconjugates were accessed.
• Tri- and tetrapeptide derivatives with non-natural cross-linking were synthesized using nucleophilic amino acids.

Conclusions:

• The reported photoredox-catalyzed method provides efficient access to N,O-acetals from peptides.
• This methodology allows for the construction of complex peptide structures and bioconjugates.
• The reaction is versatile, accommodating various nucleophilic partners including amino acid side chains for non-natural cross-linking.