Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine
Name
acsomega.1c00772.pdf
Description
Published version
Size
1.98 MB
Format
Adobe PDF
Checksum (MD5)
92bb01ba6ffa99460ab9980ae9220701
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
Date Issued
April 2021
Journal
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
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/acsomega.1c00772
