The antiviral drug Tamiflu is an important weapon in the fight against human infection with bird flu. Now Swedish chemists have developed an alternative synthesis of this drug, which should allow new analogues to be created.

Tamiflu - generically known as oseltamivir phosphate - is used for the prevention and treatment of human influenza A and B as well as for the treatment of the H5N1 avian flu virus. One of the advantages of the drug is that it can be taken orally.

Currently, commercial production of Tamiflu uses shikimic acid as a staring material, which can't be synthesised economically and has to be isolated from Chinese star anise.  The limited availability of shikimic acid has been blamed for worldwide shortages of Tamiflu.

This prompted Nina Kann at the Chalmers University of Technology, Göteborg, and colleagues to develop an alternative synthesis.

Tamiflu is a tetra-substituted cyclohexene and the key to the Kann's synthesis is the reaction of a cationic iron carbonyl complex of a cyclohexadiene with a nucleophile. By varying the nucleophile Kann anticipates that a variety of new analogues could be prepared. 

Kann hopes that this work will not only contribute to the search for novel starting materials and routes to Tamiflu but also allow diverse analogues to be prepared should resistance to the drug become more prevalent.

Nicola Burton