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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenosine Monophosphate / analogs & derivatives*
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Adenosine Monophosphate / chemical synthesis
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Adenosine Monophosphate / chemistry
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Adenosine Monophosphate / therapeutic use
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Alanine / analogs & derivatives*
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Alanine / chemical synthesis
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Alanine / chemistry
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Alanine / therapeutic use
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Amidines / chemistry*
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry*
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Antiviral Agents / therapeutic use
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COVID-19
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Chemistry Techniques, Synthetic
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Coronavirus Infections / drug therapy
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Cyclization
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Pandemics
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Pneumonia, Viral / drug therapy
Substances
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Amidines
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Antiviral Agents
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remdesivir
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Adenosine Monophosphate
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Alanine