A CONCEPTUALLY DIFFERENT APPROACH TO THE SYNTHESIS OF ENTECAVIR*
Entecavir is a nucleoside analogue 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. Although the intramolecular nitrile oxide cycloaddition (INOC) reaction has now found a wealth of application in the synthesis of heterocyclic and alkaloid systems, its use in the construction of 1-amino cyclopentane has been virtually unexplored. Herein we wish to provide an INOC-based approach to HBV inhibitor Entecavir (Scheme 1). Bromide 1 was converted to nitroalkene 2 by using sodium iodide and silver nitrte. Nitroalkene 2 was then reacted with excess p-chlorophenyl Isocyanate and a catalytic amount of Et3N to afford a single isoxazoline 3 (trans). isoxazoline 3 was transformed to intermediate 4 by hydrogenation over fresh Raney-Ni in mixture of methanol and water containing 3 equiv of acetic acid. Treatment with mesyl chloride and Et3N followed by chiral resolution gave chiral 1-amino cyclopentane 5.
HBV Entecavir Intramolecular cycloddition Isozazoline Synthesis
Ma Junan Nie Jing Li Feng
Department of Chemistry, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin Department of Chemistry, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency,Tianjin U
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
468-469
2009-09-05（万方平台首次上网日期，不代表论文的发表时间）