The Synthetic Development of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu®): A Challenge for Synthesis & Process Research


  • Stefan Abrecht
  • Peter Harrington
  • Hans Iding
  • Martin Karpf
  • René Trussardi
  • Beat Wirz
  • Ulrich Zutter



Biotechnology, Influenza neuraminidase inhibitor, Process research, Synthesis


The evolution of the synthesis of oseltamivir phosphate (Tamiflu®), used for the oral treatment and prevention of influenza virus infections (viral flu) is described. Oseltamivir phosphate is the ethyl ester prodrug of the corresponding acid, a potent and selective inhibitor of influenza neuraminidase. The discovery chemistry route and scalable routes used for kilo laboratory production as well as the technical access to oseltamivir phosphate from (–)-shikimic acid proceeding via a synthetically well-developed epoxide building block followed by azide transformations are reviewed. Synthesis and process research investigations towards azide-free conversions of the key epoxide building block to oseltamivir phosphate are discussed. The search for new routes to oseltamivir phosphate independent of shikimic acid including Diels-Alder approaches and transformations of aromatic rings employing a desymmetrization concept are presented in view of large-scale production requirements.




How to Cite

S. Abrecht, P. Harrington, H. Iding, M. Karpf, R. Trussardi, B. Wirz, U. Zutter, Chimia 2004, 58, 621, DOI: 10.2533/000942904777677605.