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

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• 作者：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 ; Chi-Huey Wong
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：October 3, 2007
• 年：2007
• 卷：129
• 期：39
• 页码：11892 - 11893
• 全文大小：88K
• 年卷期：v.129,no.39(October 3, 2007)
• ISSN：1520-5126

文摘

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.