Abstract
Remdesivir is an antiviral nucleoside phosphoramidate with activity against multiple viruses, including SARS-CoV-2. To enable studies of viral polymerases with RNA containing remdesivir, we report an efficient synthesis of a phosphoramidite of GS-441524, the nucleoside precursor of remdesivir, and its incorporation into RNA using automated solid-phase RNA synthesis.
Highlights
Remdesivir is an antiviral nucleoside phosphoramidate with activity against multiple viruses, including SARSCoV-2
This promising antiviral activity has prompted studies of viral polymerases with RNA-incorporated drug, necessitating methods to synthesize RNA containing the nucleoside precursor of remdesivir, GS-441524 (Fig. 1)
We initiated the synthesis of phosphoramidite 1 by attempting to protect the primary exocyclic amine of GS-441524 with a benzoyl group using the Jones transient N-benzoylation method, which resulted in decomposed product.[6]
Summary
Remdesivir is an antiviral nucleoside phosphoramidate with activity against multiple viruses, including SARSCoV-2. We initiated the synthesis of phosphoramidite 1 by attempting to protect the primary exocyclic amine of GS-441524 with a benzoyl group using the Jones transient N-benzoylation method (trimethylsilyl chloride, benzoyl chloride, pyridine and NH4OH), which resulted in decomposed product.[6] we altered the order of protecting group installation. Protection of the amine of 2 was optimized by reacting 2 with N,N-dimethylformamide dimethyl acetal under various reaction conditions (Table 1).
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