Efficient Synthesis of Oseltamivir Phosphate, the Active Ingredient of Tamiflu

This recent report (Angew Chem Int Ed 2009, 48, 5760-5762) from Roche process R&D describes a new and scalable synthesis starting from shikimic acid.  The paper debunks the myth, mentioned in several recent papers on Tamiflu synthesis, that shikimic acid is too expensive to use as raw material and not readily available.  In fact it is available from extraction of star anise and by fermentation.  Hundreds of tons of low cost material can now be made.  So it is the ideal starting material for the drug synthesis.

The synthesis still uses azide chemistry, pointing out that the current manufacturing method, which uses azide chemistry, has been used safely to make 100s of tonnes of the drug.  The new route is shown below