Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase
Rachel R. Knapp, Veronica Tona, Taku Okada, Richmond Sarpong, Neil K. Garg
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.
Topics & Concepts
NucleobaseChemistryYield (engineering)Combinatorial chemistryCoronavirus disease 2019 (COVID-19)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Molecule2019-20 coronavirus outbreakStereochemistryDNAVirologyBiochemistryOrganic chemistryBiologyMedicineOutbreakDiseaseInfectious disease (medical specialty)Materials scienceMetallurgyPathologyHIV/AIDS drug development and treatmentPneumocystis jirovecii pneumonia detection and treatmentBiochemical and Molecular Research