Straightforward stereoselective access to cyclic peptidomimetics

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Cyclic dipeptides (diketopiperazines) are privileged scaffolds in medicinal chemistry.
• Developing efficient synthetic routes to novel cyclic dipeptide analogs is crucial for drug discovery.
• Chiral imino lactones offer versatile starting points for complex molecule synthesis.

Purpose of the Study:

• To describe a novel synthetic strategy for preparing cyclic dipeptide mimetics.
• To explore the construction of diverse lactam ring sizes (six-, seven-, or eight-membered).
• To introduce new amino functionalities within the lactam core.

Main Methods:

• Utilized chiral imino lactones derived from (R)-phenylglycinol.
• Employed stereoselective synthesis to build a quaternary carbon center.
• Applied ring-closing metathesis (RCM) for lactam ring formation.
• Incorporated a new amino group into the lactam structure.

Main Results:

• Successfully prepared cyclic dipeptide mimetics with varying lactam ring sizes.
• Achieved fully stereoselective construction of a quaternary center.
• Demonstrated the feasibility of RCM for forming six-, seven-, and eight-membered lactams.
• Reported the synthesis of a tripeptide mimetic.

Conclusions:

• The developed synthetic route provides access to novel cyclic dipeptide mimetics.
• The methodology allows for controlled stereochemistry and structural diversity.
• This approach is valuable for generating potential therapeutic agents.