CYCLOPENTA-1,3-DIENE FOR THE SYNTHESIS OF KEY INTERMEDIATE OF ENTECAVIR*
(0) Entecavir is a nucleoside analog as a drug in treating hepatitis B viral (HBV) infections. It retains useful activity against HBV infection or co-infections with a low dose administered on a daily basis. 2+2 cycloaddition of enone and cyclopenta-1,3-diene is one of most efficient methods. Herein we reported the synthesis and separation of the key intermediate: 2-(dimethyl (phenyl)silyl)-5-formylcyclopent -3-enecarboxylic acid. Gratifyingly, the single stereoisomer was isolated from the cycloadduct by fractional recrystallization using ethyl acetate/petroleum. X-ray structure analysis revealed the trans relationship between the silyl moiety and carboxylic acid/formyl groups (Scheme 1). In addition, high yield (90%) and low enantioselectivity (19% ee) were obtained by using Cinchonine alkaloids as organocatalysts in the step of cycloaddition.
Enone Cyclopenta-1 3-diene Cycloddition HBV Entecavir
Ma Junan Liu Kun Hua Mingqing Li XiaoJuan Nie Jing
Department of Chemistry, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, Tianjin 300072, China
国际会议
International Symposium on Crystal Engineering and Drug Delivery System 2009(2009晶体工程与药物传送系统国际会议)
天津
英文
466-467
2009-09-05（万方平台首次上网日期，不代表论文的发表时间）