Design and synthesis of novel fluoro amino acids: synthons for potent macrocyclic HCV NS3 protease inhibitors

The Hepatitis C Virus (HCV) is a major health hazard and its infection is a leading cause of chronic liver disease world wide. In our efforts toward the discovery of a back up to our first clinical candidate, Boceprevir (SCH 503034), we approached the depeptidization of the molecule through macrocyclization. Herein we report the design and synthesis of fluoro amino acids with desired stereochemistry required for the synthesis of macrocyclic inhibitors with fluorine at various positions of the aliphatic chain. Biological activities of representative examples are also reported.

Graphical abstractThe design and synthesis of various fluoro amino acids required for the synthesis of new macrocyclic inhibitors are described. Biological activity of representative compounds against HCV NS3 protease is also reported.Download full-size image