Evolving to an Ideal Synthesis of Molnupiravir, an Investigational Treatment for COVID-19

Abstract

Molnupiravir (MK-4482) is an investigational direct-acting antiviral agent that is under development for the treatment of COVID-19. Given the potential high demand for this compound, it was critical to develop a sustainable and efficient synthesis from commodity raw materials. The three-step route that we report here embodies the shortest possible synthesis to molnupiravir, and was enabled through the invention of a novel biocatalytic cascade and final condensation step. Each step occurs in over 95% yield and only utilizes widely available commodity reagents and simple operations. Compared to the initial route, the new route is 70% shorter, and approximately seven-fold higher in overall yield.