阿德福韦酯的合成  

Synthesis of adefovir dipivoxil

作　　者：王晓琴[1] 何明华[1] 王勤[1] 

机构地区：[1]广东医学院药物化学与药物分析教研室,东莞523808

出　　处：《中国新药杂志》2008年第22期1937-1939,共3页Chinese Journal of New Drugs

摘　　要：目的:合成抗乙型肝炎病毒(HBV)药阿德福韦酯。方法:以腺嘌呤和三氯化磷为起始原料,分别合成9-(2-羟乙基)腺嘌呤(4)和对甲苯磺酸二乙氧基磷酰基甲酯(6),4与6在NaH作用下缩合后,经水解、酰化等反应制得阿德福韦酯。结果:文献报道的相应各步反应条件得以优化,总收率约17.5%,各中间体及产物经红外光谱、核磁共振氢谱确证。结论:本方法简化了操作步骤,优化了反应条件,降低了成本,提高了收率。Objective： To synthesize the antiviral drug adefovir dipivoxil.Methods： Starting from adenine and phosphorus trichloride,the target compound was synthesized by reaction of adenine and ethylene carbonate to form 9-（2-hydroxyethyl） adenine（4） and 4-toluenesulfonic acid diethoxyphosphorylmethyl ester（6）;then compounds（4） and（6） was subjected to condensation in presence of NaH,hydrolysis and then acylation,and finally obtained adefovir dipivoxil.Results： The total yield was 17.5%.Structures of the target product and key intermediates were verified by IR and ^1HNMR.Conclusion： This optimal synthetic procedure is simple,lower cost and higher yield.

关 键 词：阿德福韦酯 抗病毒药 乙型肝炎病毒 药物合成 

分 类 号：R978.7[医药卫生—药品] R916.41[医药卫生—药学]