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Communication

Synthesis of Tamiflu and its Phosphonate Congeners Possessing Potent Anti-Influenza Activity

Supporting Info

Jiun-Jie Shie,^† Jim-Min Fang,*^†^‡ Shi-Yun Wang,^† Keng-Chang Tsai,^† Yih-Shyun E. Cheng,^† An-Suei Yang,^† Shih-Chia Hsiao,^† Ching-Yao Su,^† and Chi-Huey Wong^†^§

The Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan. Department of Chemistry, National Taiwan University, Taipei 106, Taiwan. Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037

J. Am. Chem. Soc., 2007, 129 (39), pp 11892–11893

DOI: 10.1021/ja073992i

Publication Date (Web): September 12, 2007

†

Academia Sinica.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

National Taiwan University.

The Scripps Research Institute.

, jmfang@ntu.edu.tw

Abstract

Using d-xylose as an appropriate chiral precursor, we have synthesized active neuraminidase inhibitor oseltamivir, antiflu drug Tamiflu, and novel phosphonate congeners that exhibit even stronger antiflu activities by inhibiting the neuraminidases of the wild-type and H274Y mutant of H1N1 and H5N1 viruses. Molecular modeling of the neuraminidase−phosphonate complex indicates a pertinent binding mode of the phosphonate with three arginine residues in the active site. Discovery of such potent neuraminidase inhibitors will offer an opportunity to the development of new anti-influenza drugs.

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Accession Codes

PDB: 2HU4

History

Published In Issue October 03, 2007
Received June 1, 2007

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Communication

Synthesis of Tamiflu and its Phosphonate Congeners Possessing Potent Anti-Influenza Activity