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Cyanoamidine Cyclization Approach to Remdesivir's Nucleobase.

ABSTRACT: 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.

SUBMITTER: Knapp RR

PROVIDER: S-EPMC7653677 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Cyanoamidine Cyclization Approach to Remdesivir's Nucleobase.

Knapp Rachel R RR Tona Veronica V Okada Taku T Sarpong Richmond R Garg Neil K NK

Organic letters 20201021 21

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 remd ...[more]

PMID: 33085486

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