Oseltamivir phosphate (Tamiflu) Pt. 2
Shibasaki, Fukuta, Mita, Fukuda, Kanai. JACS, 2006, ASAP, DOI: 10.1021/ja061696k
Part-two of our flu-busting master class brings us to Shibasaki’s synthesis of Tamiflu, published, as I mentioned in the previous post, on the same day as Corey’s. This nitrogen-tastic route employs an enantioselective ring-opening of meso-aziridines with azide (hmm… don’t fancy doing that on scale…!), leading to anti-addition of nitrogen.
Using this impressive methodology, they construct the first intermediate in the scheme below, and convert to a meso diamide in five steps. The C2 symmetry was then lost by SeO2 allylic oxidation, generating the next intermediate. Addition of cyanide and asymmetric reduction generated the final stereocentre, and allowed completion of the synthesis in seven further steps.