Two research groups have published details of new synthetic routes to make Roche’s influenza drug Tamiflu, currently much in demand as governments and individuals around the world try to lay down stocks in case of a flu pandemic.
Roche has been struggling to meet burgeoning demand for Tamiflu (oseltamivir) because it is one of only two drugs that are deemed effective against avian flu strains such as H5N1, which is the front-runner among candidates to develop into a pandemic strain.
Although the company now claims to have improved supply via the creation of a network of contract manufacturers, one of the bottlenecks in production is the availability of the plant star anise, which provides one of the chemical starting materials – shikimic acid – for oseltamivir’s synthesis.
Two reports, both published in the Journal of the American Chemical Society, detail new syntheses for oseltamivir that remove the reliance on shikimic acid supply. One was developed by Masakatsu Shibasaki and colleagues at the University of Tokyo, Japan, while the other comes from Elias Corey et al of Harvard University in the USA.
Both processes make use of cheaper and more abundant starting materials, although of the two, Corey’s is believed to be more commercially viable, as it has a higher yield – about twice that currently achieved by Roche’s process – and avoids the use of hazardous intermediates.
Corey’s team has decided to place the discovery into the public domain in order to encourage other teams to work on improve the synthesis of Tamiflu and improve supply of the drug.