(R)-9-[2-(磷酸甲氧)丙基]腺嘌呤合成方法的改进

Improvement on the Synthetic Process of(R)-9-[2-(Phosphonomethoxy) Propyl] Adenine

在(R)-9-(2-羟丙基)腺嘌呤与对甲苯磺酰氧甲基磷酸二乙酯的反应中,用新鲜制备的叔丁醇锂N,N-二甲基甲酰胺溶液代替叔丁醇锂四氢呋喃溶液脱去(R)-9-(2-羟丙基)腺嘌呤中羟基上的质子,从而使得反应在较为安全的状态下进行。此外,在脱去(R)-9-[2-(二乙氧基磷酰甲氧)丙基]腺嘌呤中的乙基时,将(R)-9-[2-(二乙氧基磷酰甲氧)丙基]腺嘌呤与三甲基溴硅烷的摩尔比由原先的1∶6变化到1∶4.5。核磁共振和质谱分析表明改进后产物的化学结构与原工艺获得的产物结构相同。

A fresh-prepared solution of lithium tert-butoxide in DMF was used to replace solution of lithium tert-butoxide in THF for the deproton of hydroxyl group of （R）-9-（hydroxylpropyl） adenine, during the reaction between （R）-9-（hydroxylpropyl） adenine and diethyl p-toluenesulfonyloxymethyl phosphate. Thus, the reaction could be carried out more safely. In addition, the molar ratio of （R）-9-[2-（diethylphosphonomethoxy） propyl] adenine to trimethylsilyl bromide initially set at 1 ： 6 for the removal of two ethyl groups in （R）-9-[2-（diethylphosphonomethoxy） propyl] adenine was changed to 1： 4.5. The product was characterized by ^1H-NMR and mass spectral analysis, and the results show it is the same as that obtained by the original procedure.