Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods.

ABSTRACT: An efficient route to the HCV antiviral agent uprifosbuvir was developed in 5 steps from readily available uridine in 50% overall yield. This concise synthesis was achieved by development of several synthetic methods: (1) complexation-driven selective acyl migration/oxidation; (2) BSA-mediated cyclization to anhydrouridine; (3) hydrochlorination using FeCl₃/TMDSO; (4) dynamic stereoselective phosphoramidation using a chiral nucleophilic catalyst. The new route improves the yield of uprifosbuvir 50-fold over the previous manufacturing process and expands the tool set available for synthesis of antiviral nucleotides.

SUBMITTER: Klapars A 

PROVIDER: S-EPMC8261776 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature