Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir

Andras Horvath, Dominique Depre, Wim A. A. Vermeulen, Stijn L. Wuyts, Syuzanna R. Harutyunyan, Gregori Binot, Jef Cuypers, Wouter Couck, Dirk Van den Heuvel

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

The key macrocyclization step in the synthesis of simeprevir, a hepatitis C virus (HCV) antiviral drug, was studied. N-Boc substitution on the diene precursor changes the site of insertion of the metathesis catalyst and, consequently, the kinetic model of the ring closing metathesis (RCM), enabling a further increase in the macrocyclization efficiency under simulated high dilution (SHD) conditions. NMR of the inserted species of both first and second generation RCM catalysts are reported and discussed.

Original languageEnglish
Pages (from-to)4932-4939
Number of pages8
JournalJournal of Organic Chemistry
Volume84
Issue number8
DOIs
Publication statusPublished - 19-Apr-2019
Externally publishedYes

Keywords

  • EFFICIENT SYNTHESIS
  • HEPATITIS-C
  • MACROCYCLIZATION
  • TMC435

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