Totally Synthetic by Paul H. Docherty, 4 May 2006
Total Synthesis of Oseltamivir phosphate (Tamiflu)
Y. Fukuta, T. Mita, N. Fukuda, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2006, 128, 6312-6313.
Shibasaki’s synthesis of Tamiflu is published on the same day as Corey's. This nitrogen-rich route employs an enantioselective ring-opening of meso-aziridines with azide, 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 stereocenter, and allowed completion of the synthesis in seven further steps.