2. Academic Validation
  3. Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

  • Chem Sci. 2021 May 19;12(26):9031-9036. doi: 10.1039/d1sc01978c.
Artis Klapars 1,  John Y L Chung 1,  John Limanto 1,  Ralph Calabria 1,  Louis-Charles Campeau 1,  Kevin R Campos 1,  Wenyong Chen 1,  Stephen M Dalby 1,  Tyler A Davis 1,  Daniel A DiRocco 1,  Alan M Hyde 1,  Amude M Kassim 1,  Mona Utne Larsen 1,  Guiquan Liu 2,  Peter E Maligres 1,  Aaron Moment 1,  Feng Peng 1,  Rebecca T Ruck 1,  Michael Shevlin 1,  Bryon L Simmons 1,  Zhiguo Jake Song 1,  Lushi Tan 1,  Timothy J Wright 1,  Susan L Zultanski 1
Affiliations

Affiliations

  • 1 Department of Process Research and Development, Merck & Co., Inc. Rahway New Jersey 07065 USA [email protected].
  • 2 WuXi STA 90 Delin Road, Waigaoqiao Free Trade Zone Shanghai 200131 China.
PMID: 34276931 DOI: 10.1039/d1sc01978c
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.

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