Macrocyclization via C-H functionalization: a new paradigm in macrocycle synthesis.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Chemical Biology

Background:

• Macrocycles are crucial for targeting challenging therapeutic areas like protein-protein interactions and GPCRs.
• Developing efficient and versatile de novo macrocyclization strategies is essential for drug discovery.
• Existing methods often lack the robustness or diversity needed for complex molecular architectures.

Purpose of the Study:

• To review recent advancements in C-H activation-based macrocyclization strategies.
• To highlight the application of these methods in synthesizing complex peptides and bioactive molecules.
• To foster interest in novel macrocycle construction for organic synthesis and chemical biology.

Main Methods:

• Review of literature focusing on C-H activation logic for macrocyclization.
• Analysis of methodologies enabling access to diverse macrocycle sizes and topologies.
• Examination of applications in natural product and drug-like molecule synthesis.

Main Results:

• C-H activation offers a powerful paradigm for macrocyclization, particularly for complex peptides.
• These strategies provide high atom and step economy.
• Successful synthesis of various macrocyclic structures with diverse applications has been achieved.

Conclusions:

• C-H activation-based macrocyclization represents a significant advancement in synthetic chemistry.
• These methods facilitate efficient and diverse access to macrocycles for therapeutic applications.
• Further exploration of these techniques will drive innovation in drug discovery and chemical biology.