New and Efficient Synthesis of HCV NS3/4 A Protease Inhibitor Telaprevir

Abstract

An efficient and improved approach for the synthesis of HCV NS3/4 A (Hepatitis C virus Non‐structural protein 3) protease inhibitor, Telaprevir 1 has been developed, which involves the novel synthesis of key intermediates β‐amino‐α‐hydroxy amide 2 and tripeptide acid 3. The synthesis of β‐amino‐α‐hydroxy amide 2 was designed via the monochloro 24, dichloro 25 intermediates using the crossed Claisen condensation followed by decarboxylation with good overall yield (29.62%). The tripeptide acid 3 was developed by the coupling of dipeptide acid 20 with bicyclic nitrile 29 followed by simple chemical conversions in less number of steps with good overall yield (61.2%).

Amino Acid and Peptide‐Based Antiviral Agents

“…Several approaches leading to the production of proline‐based amino acid residue precursors have been reported. Among them, enzymatic assisted processes utilizing lipases [67] and monoamino oxidases [68] have been described.…”