O^6-(对-羧基苄基)鸟嘌呤的合成方法  

Synthesis of oncotherapeutic sensitizer O^6-(p-carboxylbenzyl) guanine

作　　者：李露[1,2] 张珩[1] 杨艺虹[1] 钟武[2] 

机构地区：[1]武汉工程大学,武汉430073 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学》2012年第5期372-375,共4页Military Medical Sciences

基　　金：国家科技支撑计划资助项目(2011BAI18B01)

摘　　要：目的合成作为肿瘤增敏剂和荧光探针分子连结子的新化合物O6-(对-羧基苄基)鸟嘌呤。方法以2-氨基-6-氯嘌呤(ACP)为起始原料,与三乙烯二胺(DABCO)反应生成DABCO-嘌呤,再进行亲核取代反应得到O6-(对-氰基苄基)鸟嘌呤这一重要中间体,最后将氰基水解为羧酸制得O6-(对-羧基苄基)鸟嘌呤。结果与结论合成获得了新结构化合物O6-(对-羧基苄基)鸟嘌呤,其结构经1H-NMR、LC-MS、13C-NMR谱得到确证,总收率为61.4%。重要中间体O6-(对-氰基苄基)鸟嘌呤的制备工艺得到优化,新工艺原料经济易得、操作简单,原子经济效率高、杂质少且易于纯化,适合工业化大生产。Objective To synthesize an oncotherapeutic sensitizer and fluorescence molecule probe connector named O6- （p-carboxylbenzyl） guanine. Methods The target compound was synthesized from ACP with DABCO to obtain DABCO- purine, O6- （p-cyanobenzyl）guanine was obtained via nucleophilic substitution reaction, and then cyano was hydrolyzed into carboxyl group to get O6- （p-carboxylbenzyl）guanine. Results and Conclusion A new-structure compound O6-（p-carboxy- lbenzyl） guanine was designed and synthesized, and the preparation technology of the important intermediate O6- （p-cyano- benzyl） guanine was optimized. The structure of the compound was confirmed by I H-NMR, LC-MS, and 13 C-NMR, and the total yield was 61.4%. The advantage of this new operational path was that the raw materials were cheap and easily availa- ble ,the operation was simple, the atomic economic efficiency was high, the impurities were little and yield was high. It＇s suitable for industrial production.

关 键 词：O6-(对-羧基苄基)鸟嘌呤 化学合成 抗肿瘤药 

分 类 号：R914[医药卫生—药物化学]