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Review
. 2021 Jul 23;6(30):19356-19363.
doi: 10.1021/acsomega.1c03082. eCollection 2021 Aug 3.

Evolution of the Synthesis of Remdesivir. Classical Approaches and Most Recent Advances

Didier F Vargas  1 , Enrique L Larghi  1 , Teodoro S Kaufman  1
Affiliations
Review

Evolution of the Synthesis of Remdesivir. Classical Approaches and Most Recent Advances

Didier F Vargas et al. ACS Omega. .

Abstract

The broad-spectrum antiviral Remdesivir, a monophosphate nucleoside analogue prodrug (ProTide), was repurposed. In May 2020, it received emergency approval by the FDA, being the first drug approved to fight the new coronavirus (COVID-19) disease which targets the virus directly. The main synthetic strategies toward Remdesivir, and their relevant modifications, are presented and discussed, to provide a panoramic view of the state-of-the-art and the more important advances in this field. Recent progress, proposed improvements, and uses of novel technologies for the synthetic sequence are also detailed.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Retrosynthetic Analysis of Remdesivir (1), Intermediate 3 (GS-441524), and Bioactive Form 4 (GS-443902)
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See this image and copyright information in PMC

References

    1. Cho A.; Saunders O. L.; Butler T.; Zhang L.; Xu J.; Vela J. E.; Feng J. Y.; Ray A. S.; Kim C. U. Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideaza adenosine C-nucleosides. Bioorg. Med. Chem. Lett. 2012, 22, 2705–2707. 10.1016/j.bmcl.2012.02.105. - DOI - PMC - PubMed
    1. Siegel D.; Hui H. C.; Doerffler E.; Clarke M. O.; Chun K.; Zhang L.; Neville S.; Carra E.; Lew W.; Ross B.; Wang Q.; Wolfe L.; Jordan R.; Soloveva V.; Knox J.; Perry J.; Perron M.; Stray K. M.; Barauskas O.; Feng J. Y.; Xu Y.; Lee G.; Rheingold A. L.; Ray A. S.; Bannister R.; Strickley R.; Swaminathan S.; Lee W. A.; Bavari S.; Cihlar T.; Lo M. K.; Warren T. K.; Mackman R. L. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f]triazin-4-amino adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J. Med. Chem. 2017, 60, 1648–1661. 10.1021/acs.jmedchem.6b01594. - DOI - PubMed
    1. Wang Z.; Yang L. GS-5734: FDA potentially approved drug against SARS-Cov-2. New J. Chem. 2020, 44, 12417–12429. 10.1039/D0NJ02656E. - DOI
    1. Food and Drug Administration . Coronavirus (COVID-19) update: FDA issues emergency use authorization for potential COVID-19 treatment; Washington DC, USA, 2020.
    1. Eastman R. T.; Roth J. S.; Brimacombe K. R.; Simeonov A.; Shen M.; Patnaik S.; Hall M. D. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Cent. Sci. 2020, 6, 672–683. 10.1021/acscentsci.0c00489. - DOI - PMC - PubMed