Application of ring-closing metathesis for the synthesis of macrocyclic peptidomimetics as inhibitors of HCV NS3 protease

Org Lett. 2007 Aug 2;9(16):3061-4. doi: 10.1021/ol0711265. Epub 2007 Jul 4.

Abstract

An efficient synthetic approach for the preparation of macrocyclic peptidomimetics for inhibition of HCV NS3 is presented. The macrocyclic core is built using ring-closing metathesis (RCM) of a tripeptidic diene. The presented approach allows the introduction of heteroatoms in strategic places along the macrocyclic ring. The methyl ester moiety in the RCM products was synthetically manipulated to install a keto-amide moiety via a Passerini reaction.

MeSH terms

  • Catalysis
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Hepacivirus / enzymology*
  • Molecular Mimicry
  • Molecular Structure
  • Peptides / chemistry*
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology

Substances

  • Enzyme Inhibitors
  • Peptides
  • Pyrroles