Synthesis Of Influenza Neuraminidase Inhibitor Oseltamivir

Oseltamivir (1), an influenza neuraminidase inhibitor, was developed by Gilead Science Inc. and then licensed to F. Hoffmann-La Roche Ltd. for co-development and marketing worldwide. It was first launched as Tamiflu^? in Switzerland in October 1999 for the treatment of influenza caused by the influenza virus A and B. Recently, 1 is also used as an efficient drug to bird influenza.Some influenza neuraminidase inhibitor agents were reviewed in this thesis. Starting from (-)-shikimic acid, oseltamivir was prepared via 11-step sequence in a total yield of 8.5%, one fold higher than that of the reported. The structure of the target molecule was determined by ¹H NMR, ¹³CNMR and ESI-MS.The process of preparing compound 39 was cost-effective due to the use of triphenylphosphine instead of trimethylphosphine. The work-up procedure in this step was simplified. The processes to prepare compound 5 and 7 were also optimized and higher yield was obtained.Most of the reactions involved are mild and easily put in practice. This process has an economic advantage in view of the application for large-scale synthesis.