Synthesis of a macrocyclic and medium-sized ring lactam library using cascade ring expansion reactions

Area of Science:

• Organic synthesis
• Medicinal chemistry
• Chemical biology

Background:

• Lactam compounds are important scaffolds in medicinal chemistry.
• Developing efficient synthetic routes for diverse lactam libraries is crucial for drug discovery.
• Antibacterial drug discovery remains a critical area of research.

Purpose of the Study:

• To develop a versatile synthetic approach for generating diverse libraries of macrocyclic and medium-sized ring lactams.
• To evaluate the antibacterial activity of the synthesized lactam library against Staphylococcus aureus and Escherichia coli.

Main Methods:

• A three-step sequential synthesis involving conjugate addition/ring expansion cascade.
• Subsequent side-chain and ring elaboration steps to diversify the lactam structures.
• Bioassay screening of the generated library for antibacterial activity.

Main Results:

• A diverse library of macrocyclic and medium-sized ring lactams was successfully synthesized.
• The synthesized compounds were tested against Staphylococcus aureus and Escherichia coli.
• No novel antibacterial agents were identified in this specific library.

Conclusions:

• The developed synthetic approach is effective for the rapid generation of diverse lactam libraries.
• This methodology is valuable for high-throughput screening in antibacterial drug discovery programs.
• Further optimization and derivatization may be necessary to identify potent antibacterial compounds.