ABSTRACT
The SARS-CoV-2 pandemic has prompted scientists from many disciplines to work collaboratively toward an effective response. As academic synthetic chemists, we examine how best to contribute to this ongoing effort.
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.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amidines/chemistry , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Adenosine Monophosphate/chemical synthesis , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/therapeutic use , Alanine/chemical synthesis , Alanine/chemistry , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Chemistry Techniques, Synthetic , Coronavirus Infections/drug therapy , Cyclization , Pandemics , Pneumonia, Viral/drug therapyABSTRACT
The SARS-CoV-2 pandemic has prompted scientists from many disciplines to work collaboratively toward an effective response. As academic synthetic chemists, we examine how best to contribute to this ongoing effort.