Production of oseltamivir and additional antiviral compounds
Project No. 2012
Principal Investigator/Inventor: Dr. Tomas Hudlicky, Department of Chemistry
A method for the production of oseltamivir, novel oseltamivir intermediates and additional antiviral compounds, their synthesis, and their use as anti-viral agents.
In response to the potential bird flu human influenza pandemic, Hoffman-La Roche developed oseltamivir (Tamiflu®). Oseltamivir is an antiviral drug used in the treatment and prophylaxis of both influenza virus A and influenza virus B. In 2007 Roche was producing 400 million doses of Tamiflu® with a market value of $2.2 billion. The commercial method of production of Tamiflu® involves shikimis acid during manufacturing, a highly expensive compound in limited supply with decreasing availability as demand for Tamiflu® increases. Dr. Hudlicky has developed a method for synthesis of oseltamivir and its precursor intermediates that utilizes readily available precursors (i.e. commodity chemicals). The method comprises five operations; current syntheses require from 8-21 steps. This allows for much more cost-effective large-scale oseltamivir production using an azide-free process. Additionally, a number of novel intermediate molecules, structurally similar to Tamiflu®, can be produced with potentially more desirable pharmacologic and efficacy characteristics.
Hudlicky et al., “Processes for the preparation of Tamiflu and analogs thereof and intermediates thereof.” Applications in: US 61/052435, 12/992024, 13/502375; PCT CA2009/000622, CA2010/001639; Canada 2777187.
Sullivan, B., et al., (2009) Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (Tamiflu) from ethyl benzoate. Angew. Chem. Int. Ed. Engl. 48: 4229-31.