Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine
Author(s)
Ahlqvist, Grace P.; McGeough, Catherine P.; Senanayake, Chris; Armstrong, Joseph D.; Yadaw, Ajay; Roy, Sarabindu; Ahmad, Saeed; Snead, David R.; Jamison, Timothy F; ... Show more Show less
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Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on a decagram scale: the first step at 200 g and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Date issued
2021-04Department
Massachusetts Institute of Technology. Department of ChemistryJournal
ACS Omega
Publisher
American Chemical Society (ACS)
Citation
Ahlqvist, Grace P. et al. "Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine." ACS Omega 6, 15 (April 2021): 10396–10402. © 2021 The Authors
Version: Final published version
ISSN
2470-1343
2470-1343