Improved synthesis of rupintrivir.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Drug Discovery

Background:

• Rupintrivir (AG7088) is a significant antiviral agent.
• Efficient synthesis pathways are crucial for drug development and accessibility.

Purpose of the Study:

• To establish an improved and efficient synthetic route for rupintrivir (AG7088).
• To utilize amino acids as cost-effective and accessible building blocks.

Main Methods:

• The synthesis involved constructing a ketomethylene dipeptide isostere using valine and phenylpropionic acid derivatives.
• Subsequent coupling reactions with a lactam derivative and an isoxazole acid chloride were performed.
• The entire synthesis was completed in eight steps.

Main Results:

• An optimized eight-step synthesis of rupintrivir (AG7088) was successfully achieved.
• The synthesis employed l-glutamic acid, d-4-fluorophenylalanine, and l-valine as primary building blocks.
• Key intermediates, including a ketomethylene dipeptide isostere, were efficiently prepared.

Conclusions:

• The developed synthetic strategy provides a streamlined and effective method for producing rupintrivir (AG7088).
• This improved synthesis offers a viable route for the large-scale production of this important antiviral compound.