Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase

[Image: see text] We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formatio...

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Autores principales: Knapp, Rachel R., Tona, Veronica, Okada, Taku, Sarpong, Richmond, Garg, Neil K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653677/
https://www.ncbi.nlm.nih.gov/pubmed/33085486
http://dx.doi.org/10.1021/acs.orglett.0c03052
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author Knapp, Rachel R.
Tona, Veronica
Okada, Taku
Sarpong, Richmond
Garg, Neil K.
author_facet Knapp, Rachel R.
Tona, Veronica
Okada, Taku
Sarpong, Richmond
Garg, Neil K.
author_sort Knapp, Rachel R.
collection PubMed
description [Image: see text] We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics.
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spelling pubmed-76536772020-11-12 Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase Knapp, Rachel R. Tona, Veronica Okada, Taku Sarpong, Richmond Garg, Neil K. Org Lett [Image: see text] We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics. American Chemical Society 2020-10-21 2020-11-06 /pmc/articles/PMC7653677/ /pubmed/33085486 http://dx.doi.org/10.1021/acs.orglett.0c03052 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Knapp, Rachel R.
Tona, Veronica
Okada, Taku
Sarpong, Richmond
Garg, Neil K.
Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title_full Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title_fullStr Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title_full_unstemmed Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title_short Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
title_sort cyanoamidine cyclization approach to remdesivir’s nucleobase
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653677/
https://www.ncbi.nlm.nih.gov/pubmed/33085486
http://dx.doi.org/10.1021/acs.orglett.0c03052
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