Why did the chicken cross the road?
With H5N1 avian influenza gradually making its way across the world, a lot of people are preparing for the worst. It's still not clear if this strain of the flu will 'evolve the ability to spread between people,' but if this happens, we're in for some serious problems:
The current syntheses of oseltamivir (a.k.a. Tamiflu) fall 'short of the ideal for several reasons: (1) the starting point in the synthesis is either (-)-shikimic or (-)-quinic acid, which are complex relatively expensive and of limited availability, and (2) two steps involve potentially hazardous and explosive azide-containing intermediates.'
But two new syntheses of oseltamivir/Tamiflu were reported in JACS earlier this week: one is by Yeung et al. and the other is by Fukuta et al.
Although the synthesis from Corey's group is much shorter, both syntheses avoid using either (-)-shikimic or (-)-quinic acid as starting materials: Corey's synthesis starts with 1,3-butadiene and trifluoroethyl acrylate and Shibasaki's synthesis starts with the asymmetric ring-opening reaction of a meso-aziridine with TMSN3. If these syntheses could be scaled up and optimized further, it might be possible to reduce the cost of oseltamivir/Tamiflu and pharmaceutical companies (or paranoid graduate students) could make plenty of the compound, which could be stockpiled and used if a human pandemic occurs.
The only catch: oseltamivir-resistant virus has already been reported in Vietnam...
Joshua
Joshua Finkelstein (Associate Editor, Nature)
Comments
The emergence of Tamiflu-resistant strain may raise two fundamentally related issues: i) discovery of new antiviral drug, whether the analogues of Tamiflu or not; ii) the way evaluating multi-step synthesis; i.e., recent practical view of "process-ibilty" or rather obsolete view about "elegance" and/or "creativity". Though it may sound presumptuous, i'd like to say neither of views really helps the discovery of "new-Tamiflu". for example, the flexibilty of synthetic pathway incorporating diverse elements - depending on the response of resistant strain - can be more important than the number of steps and others.
Posted by: NoName | April 30, 2006 11:53 PM
Update: There was a news story in Science on these papers on the 26th and CE&N published a story on this yesterday.
Posted by: Joshua | May 2, 2006 09:32 AM
Not to smear anyone here, but when I worked for big pharma there was a saying about Corey Chemistry and it's usefulness outside of Harvard and it was not a flattering saying.... I will wait to see if the Corey results can be replicated outside of Cambridge.
Posted by: Organic Chemistry | January 19, 2007 04:55 PM