Solid-Phase Parallel Synthesis of Functionalised Medium-to-Large Cyclic Peptidomimetics through Three-Component...

Area of Science:

• Organic Chemistry
• Peptide Chemistry
• Synthetic Chemistry

Background:

• Macrocyclic peptides are important in drug discovery.
• Efficient synthesis of diverse macrocyclic peptides remains a challenge.

Purpose of the Study:

• To describe the first solid-phase parallel synthesis of macrocyclic peptides using aziridine aldehyde dimers.
• To enable rapid and diverse synthesis of aziridine-containing macrocycles.

Main Methods:

• Solid-phase synthesis.
• Three-component coupling reaction.
• Aziridine aldehyde dimers as key building blocks.
• Nucleophilic opening of aziridine ring for functionalization.

Main Results:

• Successful synthesis of 9- to 18-membered aziridine-containing macrocycles.
• Demonstration of a robust and rapid parallel synthesis approach.
• Versatile functionalization via aziridine ring opening.

Conclusions:

• A novel and efficient method for macrocyclic peptide synthesis has been established.
• This approach facilitates the rapid generation of diverse macrocyclic peptide libraries.
• The methodology holds promise for drug discovery and chemical biology applications.