Synthesis of azole-enriched cyclic peptides by a clean solid-phase-based cyclization-cleavage strategy

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Naturally occurring azole-enriched cyclic peptides exhibit diverse biological and pharmacological activities.
• Previous synthetic routes focused on individual molecule preparation in solution phase.
• Multidrug resistance (MDR) efflux proteins are key targets for therapeutic intervention.

Discussion:

• A novel solid-phase cyclitive cleavage strategy was employed for efficient library synthesis of azole cyclopeptide derivatives.
• Optimization of procedures resulted in high yield and purity of azole cyclopeptides.
• This approach eliminates the need for chromatographic purification, streamlining the synthesis process.

Key Insights:

• The developed solid-phase strategy enables high-throughput library synthesis of azole cyclopeptides.
• The method facilitates the characterization of potent modulators of multidrug resistance efflux proteins.
• High purity and yield simplify downstream screening and characterization.

Outlook:

• This strategy is ideal for accelerating the discovery of novel azole cyclopeptides.
• Further exploration of these compounds may lead to new therapeutic agents against multidrug resistance.
• The methodology can be applied to the synthesis of other complex cyclic peptide libraries.