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.
A scalable four-step
synthesis of molnupiravir from cytidine is
described herein. The attractiveness of this approach is its fully
chemical nature involving inexpensive reagents and more environmentally
friendly solvents such as water, isopropanol, acetonitrile, and acetone.
Isolation and purification procedures are improved in comparison to
our earlier study as all intermediates can be isolated via recrystallization.
The key steps in the synthesis, namely, ester formation, hydroxyamination,
and deprotection were carried out on a multigram scale to afford molnupiravir
in 36–41% yield with an average purity of 98 wt % by qNMR and
99 area% by HPLC.
Some ruthenium(III) complexes with aryl-azo 2,4-pentanedione as co-ligands (L1H - L3H2) have been synthesized and characterized spectroscopically IR, 1H NMR, UV/Vis, ESR, conductimetric)
along with elemental analysis and FAB-mass data. Their luminescent and redox properties have
been studied. The antibacterial, anti-HIV and antitmnour activities have also been reported.
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