Rh(III)-Catalyzed Double C-H Activation toward Peptide-Benzazepine Conjugates

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Catalysis

Background:

• Peptide-benzazepine conjugates are complex molecules with potential therapeutic applications.
• Efficient synthetic routes are crucial for exploring their biological activities.
• C-H activation offers a powerful strategy for constructing complex molecular architectures.

Purpose of the Study:

• To develop an efficient and selective method for synthesizing peptide-benzazepine conjugates.
• To explore the antifungal activity of the synthesized conjugates.
• To demonstrate the synthetic utility and scalability of the developed method.

Main Methods:

• Rh(III)-catalyzed double C-H activation reaction between Lys-based peptides and acroleins.
• Optimization of reaction conditions for efficiency and selectivity.
• Scale-up experiments and late-stage derivatizations.
• Preliminary antifungal activity screening against pathogenic fungi.

Main Results:

• Efficient synthesis of peptide-benzazepine conjugates achieved under mild conditions.
• The reaction exhibited broad scope, high atom and step economies, and excellent chemo- and site selectivity.
• Successful scale-up and derivatization of the synthesized conjugates.
• Demonstrated good antifungal activity of the conjugates against crop and forest pathogenic fungi.

Conclusions:

• The developed Rh(III)-catalyzed double C-H activation is an efficient and versatile method for synthesizing peptide-benzazepine conjugates.
• The synthesized conjugates possess significant potential as antifungal agents for agricultural and forestry applications.
• This strategy provides a valuable platform for further drug discovery and development in this area.