Study On Synthesis Of Telaprevir

Abstract：Hepatitis C (HC) is a kind of hepatic disease which is caused by hepatitis cvirus (HCV). The epidemicity of HCV is really strong and the health problems fromHCV have attracted great attention. Telaprevir (VX-950) is a kind of new drugdeveloped by Vertex Phamaceutical Company in America for treating HC. It waspermitted by FDA to come into the market in2011with a trade name Incivek. Thismedicine of the oral dosage form is a kind of reversible calcineurin inhibitor, whichcan be used together with PEG IFNα and Ribavirin to prevent the copy of HCV viruseffectively for being suitable to treat HC, which possesses promising future.In this paper, on the one hand, we employed the synthetic route reported by therelevant patents to synthesize Telaprevir successfully, the synthetic conditons wereoptimized and the purity detection using HPLC was proposed. On the other hand, inorder to develop new synthetic technology of Telaprevir, we designed two novelsynthetic routes which have not been reported followed by the study of theireffectiveness. First pyrazinyl-2-carboxylic acid and L-cyclohexylglycine were usedas the starting materials, after several steps including the protection of functionalgroups, the formation of peptide bonds and hydrolytic reactions, a series ofintermediates of Telaprevir were synthesized with high yields. These interdiates werecharacterized by MS and NMR. This work provides valuable references for futher todevelop the synthetic processes of Telaprevir.