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> |
申请人 |
WONG, CHI-HUEY;FANG, JIM-MIN;SHIE, JIUN-JIE;CHENG, YIH-SHYUN, EDMOND;JAN, JIA-TSRONG |
发明人 |
WONG, CHI-HUEY;FANG, JIM-MIN;SHIE, JIUN-JIE;CHENG, YIH-SHYUN, EDMOND;JAN, JIA-TSRONG |