Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease.

@article{Chen2005SynthesisAB,
  title={Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease.},
  author={Kevin X Chen and F. George Njoroge and Andrew J. Prongay and John S Pichardo and Vincent S. Madison and Viyyoor M. Girijavallabhan},
  journal={Bioorganic & medicinal chemistry letters},
  year={2005},
  volume={15 20},
  pages={4475-8}
}
The 17-membered phenylalanine-based macrocycle 6 was prepared starting from 3-iodo-phenylalanine. Macrocyclization of alkene phenyl iodide 5 was effected through a palladium-catalyzed Heck reaction. The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters.