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. 2022 Oct 21;12(46):30120-30124.
doi: 10.1039/d2ra05064a. eCollection 2022 Oct 17.

Concise two-step chemical synthesis of molnupiravir

Vinícius R D Pereira  1 , Marco A M Bezerra  2 , Mauro R B P Gomez  2 , Guilherme M Martins  3 , Adilson D da Silva  1 , Kleber T de Oliveira  3 , Rodrigo O M A de Souza  2 , Giovanni W Amarante  1
Affiliations

Concise two-step chemical synthesis of molnupiravir

Vinícius R D Pereira et al. RSC Adv. .

Abstract

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Chemical routes to molnupiravir (2).
Scheme 2
Scheme 2. Batch cetalization process of uridine (1).
Scheme 3
Scheme 3. One-pot cetalization and esterification processes of the uridine (1).
Scheme 4
Scheme 4. One-pot oxyamination/deprotection reaction to molnupiravir (2).
Fig. 1
Fig. 1. Molnupiravir (2) HPLC analysis conditions: mobile phase A: 40 mM ammonium dihydrogen phosphate aqueous solution; mobile phase B: methanol; column: Agilent Eclipse XDB-C18, 4.6 × 150 mm, 5 μm; injection volume: 10 μL, detector: DAD (260 nm).
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References

    1. WHO, WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int/, accessed May 31th, 2022
    1. Harvey W. T. Carabelli A. M. Jackson B. Gupta R. K. Thomson E. C. Harrison E. M. Ludden C. Reeve R. Rambaut A. Peacock S. J. Nat. Rev. Microbiol. 2021;19:409–424. doi: 10.1038/s41579-021-00573-0. - DOI - PMC - PubMed
    1. Syed Y. Y. Drugs. 2022;82:455–460. doi: 10.1007/s40265-022-01684-5. - DOI - PMC - PubMed
    1. Kabinger F. Stiller C. Schmitzová J. Dienemann C. Kokic G. Hillen H. S. Höbartner C. Cramer P. Nat. Struct. Mol. Biol. 2021;28:740–746. doi: 10.1038/s41594-021-00651-0. - DOI - PMC - PubMed
    1. Braga T. C. Santos J. A. Castro P. P. Amarante G. W. Quim. Nova. 2022;45:53–73.