Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP

James M. Wood, Gary B. Evans, Tyler L. Grove, Steven C. Almo, Scott A. Cameron, Richard H. Furneaux, Lawrence D. Harris

Research output: Contribution to journalArticlepeer-review

Abstract

3′-Deoxy-3′,4′-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin as part of the innate immune response. ddhCTP has been shown to act as an obligate chain terminator of flavivirus and SARS-CoV-2 RNA-dependent RNA polymerases; however, further biophysical studies have been precluded by limited access to this promising antiviral. Herein, we report a robust and scalable synthesis of ddhCTP as well as the mono-and diphosphates ddhCMP and ddhCDP, respectively. Identification of a 2′-silyl ether protection strategy enabled selective synthesis and facile purification of the 5′-Triphosphate, culminating in the preparation of ddhCTP on a gram scale.

Original languageEnglish (US)
Pages (from-to)8843-8850
Number of pages8
JournalJournal of Organic Chemistry
Volume86
Issue number13
DOIs
StatePublished - Jul 2 2021

ASJC Scopus subject areas

  • Organic Chemistry

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