Peptide Stapling with Anion-π Catalysts.

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Catalysis

Background:

• Peptide stapling is a technique to stabilize peptide secondary structures.
• Naphthalenediimides (NDIs) are electron-deficient aromatic systems with potential catalytic applications.
• Anion-π catalysis utilizes electron-deficient surfaces to activate anions.

Purpose of the Study:

• To synthesize and evaluate naphthalenediimide (NDI)-stapled peptides as novel catalysts.
• To investigate the influence of peptide structure on anion-π catalysis.
• To explore the potential of these systems for selective chemical transformations.

Main Methods:

• Design and synthesis of NDI-peptide conjugates via nucleophilic aromatic substitution.
• Separation and characterization of atropisomers.
• Evaluation of catalytic activity in benchmark enolate chemistry reactions.
• Structure-activity relationship studies.

Main Results:

• NDI-stapled peptides were successfully synthesized and exist as separable atropisomers.
• The introduction of tertiary amine bases enabled anion-π catalysis.
• Record chemoselectivity was achieved in enolate reactions, though enantioselectivity was weak.
• Catalytic activity was sensitive to structural modifications, with longer α-helices showing increased performance.

Conclusions:

• NDI-stapled peptides are effective anion-π catalysts with tunable activity.
• Peptide secondary structure, particularly α-helix formation, significantly enhances catalytic efficiency.
• These findings open avenues for developing sophisticated peptide-based catalytic systems.