New method for synthesising Tamiflu

Elias Corey, the 1990 Nobel laureate in Chemistry, and two of his students have worked out a new synthesis pathway for the anti-flu drug Tamiflu (oseltamivir).

The new method requires simpler starting compounds, namely 1,3-butadiene and acrylic acid, both of which are used in common industrial reactions for producing polymers, whereas the commercial method used by the pharmaceutical company Roche requires shikimic acid, which is extracted from the spice plant star anise. Furthermore, the yield for the new method is good, explosive intermediates (which pose a danger in the manufacturing process and hence drive up costs and production time/bulk) are avoided, and the use of what the authors call "a novel SnBr4-catalyzed bromoacetamidation reaction which was completely regio- and stereoselective" (between products 9 and 10 in the diagram) eliminates the problem of undesired enantiomers, i.e. similar molecules with the same parts oriented in the wrong way. In pharmaceutical compounds, molecular shape is important because drugs work through molecular recognition and binding, which would not occur if the chemical formula is correct but the wrong stereoisomer is used. More commonly, both the 'correct' and 'incorrect' form are produced simultaneously by synthetic methods which do not differentiate between the two forms, thus producing a mixture. In rare cases the wrong isomer might even have toxic effects, while the chemical similarity of the two isomeric forms make them hard to separate from each other. Therefore, a regio- and stereo-selective catalyst is a very fortunate discovery.

In their paper, the authors Yeung, Hong, and Corey are optimistic about scaling up the process to industrial level. Hopefully, this might reduce the cost of Tamiflu production and make it more accessible to poorer countries where the threat of bird flu is greater. It's also worth pointing out that they did their work independently of Roche, which manufactures Tamiflu, save for obtaining a sample of the compound for comparison and identification of their product. In problems of great import, perhaps such a problem-solving model is more effective, viz. welcoming solutions from private individuals and academia alongside commercial and government agencies, because as the proverb goes, more hands make light work. It's ironic, and a little bit sad, that the Age of the Amateur has not really taken off despite all the opportunities for communication and the widespread availability of information around the world today. Most of us are pretty passive about the technologies and processes that affect us, and very few people take an interest in tinkering and working to find better solutions for themselves, more adapted to their local and personal situations. It's easy to blame commerce and industry, which produce neatly packaged, tamper-proof products that consumers treat like black boxes: they see the input and see the output but don't really care about what goes on inside to change one to the other. In the case of computer and software technology, tinkering is actually discouraged by commercial interests, who have taken the appellation 'hacking', which originally referred to enthusiasts toying with and modifying computer code, and made it into a fearsome nebulous term that is equated with malicious infringement of privacy and wilful wrongdoing. More people should take an interest in how things work, so that with the vast quantity of untapped intellectual potential out there (people whose intellects are underemployed, or who have free time to pursue hobbies and interests), a form of distributed computing can be applied to the thinking populace and a culture of innovation can develop.