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Issue 26, 2021

Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

Author affiliations

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.

Graphical abstract: Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

Supplementary files

Article information


Submitted
08 Apr 2021
Accepted
17 May 2021
First published
19 May 2021

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2021,12, 9031-9036
Article type
Edge Article

Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

A. Klapars, J. Y. L. Chung, J. Limanto, R. Calabria, L. Campeau, K. R. Campos, W. Chen, S. M. Dalby, T. A. Davis, D. A. DiRocco, A. M. Hyde, A. M. Kassim, M. U. Larsen, G. Liu, P. E. Maligres, A. Moment, F. Peng, R. T. Ruck, M. Shevlin, B. L. Simmons, Z. J. Song, L. Tan, T. J. Wright and S. L. Zultanski, Chem. Sci., 2021, 12, 9031 DOI: 10.1039/D1SC01978C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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