Synthesis of molnupiravir (MK-4482, EIDD-2801): a promising oral drug for the treatment of COVID-19 starting from cytidine

The present work describes the synthesis of molnupiravir by employing commercially available inexpensive materials in two steps with an overall yield of 85.7%. The synthetic methodology starts with an eco-friendly starting material, that is, cytidine and establishes an alternative way to avoid costly enzyme mediated reactions. This synthetic strategy involves a selective acylation of cytidine as the first key step followed by the second step, that is, hydroxamination reaction. The major advantage of this protocol is that it is completely free of protection and deprotection reactions. Chemoselective acylation of cytidine's primary alcohol was achieved using isobutyryl chloride, Et₃N, and DMF solvent (89.3% yield). The aqueous phase transformation was achieved for the hydroxamination reaction with a 96% yield.