发明名称 |
SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY |
摘要 |
<p>Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5 -cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.</p> |
申请公布号 |
EP2190439(A4) |
申请公布日期 |
2013.02.20 |
申请号 |
EP20080828468 |
申请日期 |
2008.08.29 |
申请人 |
ACADEMIA SINICA |
发明人 |
FANG, JIM-MIN;SHIE, JIUN-JIE;WONG, CHI-HUEY;CHENG, YIH-SHYUN EDMOND;JAN, JIA-TSRONG |
分类号 |
A61K31/7076;A61K9/16;A61K31/7052;C07C233/52;C07C247/14;C07H19/04 |
主分类号 |
A61K31/7076 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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