From Batch to Continuous Flow Synthesis in Enzymatic Process Towards Molnupiravir.

Area of Science:

• Biocatalysis and Organic Synthesis
• Medicinal Chemistry and Drug Development
• Chemical Engineering and Process Optimization

Background:

• Molnupiravir is a crucial antiviral medication for COVID-19 treatment.
• The COVID-19 pandemic necessitated rapid development of efficient drug synthesis methods.
• Existing molnupiravir synthesis routes required optimization for large-scale production.

Purpose of the Study:

• To develop a facile, scalable, and efficient synthesis of molnupiravir.
• To implement continuous flow biocatalysis for enhanced production efficiency.
• To compare batch and continuous flow processes for molnupiravir synthesis.

Main Methods:

• A 2-step synthesis involving transamination of cytidine and regioselective esterification.
• Utilized immobilized lipase and isobutyric anhydride for esterification.
• Implemented both batch processing and continuous flow biocatalysis.

Main Results:

• Achieved 48% overall yield and 99.98% purity for molnupiravir via batch processing.
• Continuous flow biocatalysis demonstrated comparable yield and purity.
• Continuous flow offered significant advantages: 2.42-fold higher productivity, 2.47-fold faster reaction time, and 30-fold higher space-time-yield.

Conclusions:

• Optimized batch and continuous flow biocatalysis enhance molnupiravir synthesis efficiency.
• Continuous flow biocatalysis presents a more productive and time-efficient method.
• These optimized processes offer a sustainable approach for industrial molnupiravir production with reduced environmental impact.