Pilot-Scale Lipase-Catalyzed Regioselective Acylation of Ribavirin in Anhydrous Media in the Synthesis of a Novel Prodrug Intermediate

Abstract

The ester 4 was synthesized via Candida antarctica lipase-catalyzed acylation of ribavirin (3) with the oxime ester of l-Cbz-Ala (2) in anhydrous THF. The reaction was highly regioselective, resulting in the exclusive acylation of the 5‘-hydroxyl. The process practiced on pilot-plant scale produced 82 kg of 4 in three batches in an average isolated yield of 82%.