Contributor(s): Philip Kocienski
Gopalsamuthiram V. et al.
Medicines for All Institute, Richmond, USA
Org. Process Res. Dev. 2021;
25: 2679-2685
DOI: 10.1021/acs.oprd.1c00219.
Key words
molnupiravir - COVID-19 - nucleosides - hydroxyamination
Significance
Molnupiravir (MK-4482) inhibits viral reproduction of coronaviruses including SARS, MERS, and SARS-CoV-2 by promoting widespread mutations in the replication of viral RNA by RNA-directed RNA polymerase. It was approved in the UK in November 2021 for treating adults with mild to moderate symptoms who are at high risk of developing severe COVID-19.
Comment
The chromatography-free, four-step synthesis of molnupiravir depicted (36–41% overall yield) starts with inexpensive cytidine. All the intermediates in this route were purified by crystallization. For an alternative two-step process for the synthesis of molnupiravir from cytidine that includes a direct hydroxyamination reaction as a key step, see: Org. Process Res. Dev. 2021, 25, 1822, highlighted in Synfacts 2021, 17, 1190.
