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

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 α-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters.