Methionine-enabled peptide modification through late-stage Pd-catalyzed β-C(sp³)-H olefination/cyclization

Area of Science:

• Organic Chemistry
• Peptide Chemistry
• Catalysis

Background:

• Peptide modification is crucial for drug discovery and materials science.
• Site-selective functionalization remains a challenge in peptide chemistry.
• Current methods often lack efficiency or require protecting groups.

Purpose of the Study:

• To develop a novel method for site-selective peptide diversification.
• To utilize native amino acid residues as directing groups.
• To establish a versatile platform for peptide ligation.

Main Methods:

• Palladium-catalyzed β-C(sp3)-H olefination and cyclization reactions.
• Employing the native methionine residue as a directing group.
• Optimization of reaction conditions for efficient peptide modification.

Main Results:

• Achieved site-selective olefination/cyclization at the methionine residue.
• Demonstrated broad substrate scope for various peptide sequences.
• Successfully applied the method for peptide ligation applications.

Conclusions:

• The developed method offers a powerful tool for site-specific peptide diversification.
• This approach simplifies peptide modification by leveraging native residues.
• The chemistry provides a versatile strategy for constructing complex peptide conjugates.