Synfacts 2008(2): 0119-0119  
DOI: 10.1055/s-2007-992507
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Tamiflu

Contributor(s):Philip Kocienski
J.-J. Shie, J.-M. Fang*, S.-Y. Wang, K.-C. Tsai, Y.-S. E. Cheng, A.-S. Yang, S.-C. Hsiao, C.-Y. Su, C.-H. Wong
National Taiwan University and Academia Sinica, Taipei, Taiwan; The Scripps Research Institute, La Jolla, USA
Synthesis of Tamiflu and Its Phosphonate Congeners Possessing Potent Anti-Influenza Activity
J. Am. Chem. Soc.  2007,  129:  11892-11893  
Further Information

Publication History

Publication Date:
23 January 2008 (online)


Significance

Drug resistance and side effects in children observed with tamiflu motivated this search for new neuraminidase inhibitors directed towards a treatment for avian influenza. Conventional methodology was used to convert d-xylose into tamiflu as well as some phosphonate congeners (e.g., tamiphosphor and I).

Comment

The phosphonate congeners are significantly more potent than the carboxylate congeners against the wild-type neuraminidases H1N1 and H5N1. Moreover, analogue I is a 19 nM inhibitor for the H274Y mutant of H5N1 neuramindase.