Recent Progress on the Total Synthesis of (–)-Oseltamivir Phosphate (Tamiflu) for the Treatment of Influenza Disease

Influenza can affect the health of human being and it is considered as the most serious respiratory disease. (–)-Oseltamivir phosphate, also popularly known as Tamiflu, has been reported to be one of the most potent chemotherapeutic agents with oral activity. It can inhibit the viral neuraminidase enzyme to catalyze the cleavage of the sialic acid residue from glycoproteins, thus preventing the infected cells to liberate the proliferated viruses. The industrial production method for oseltamivir phosphate uses (–)-shikimic acid as the starting material, which is a natural product isolated from a plant of Chinese star anise (belonging to the Illicium family). However, because the (–)-shikimic acid is unavailable in consistent purity and sufficient quantity, many chemists have dedicated some new synthetic routes to prepare this drug for the treatment of influenza disease. In this article, the reported synthetic approaches for (–)-oseltamivir phosphate since 2011 are reviewed, and the representative results are described in chronological order.