一种基于硫胺素二硫化物传递系统的5-Fu脑靶向前药的合成  

Synthesis of the brain-targeted prodrug of 5-fluorouracil based on thiamine disulfide

作　　者：陈瑶瑶[1] 樊维[1] 余永国[1] 吴勇[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2010年第2期123-125,共3页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:30672537)

摘　　要：目的合成一种基于硫胺素二硫化物传递系统的5-氟尿嘧啶(5-Fu)脑靶向前药。方法5-Fu在六甲基二硅胺和三甲基氯硅烷的作用下生成中间体Ⅱ,Ⅱ与5-苄氧羰基戊酰氯经选择性酰化形成中间体Ⅲ,Ⅲ再脱苄,得到中间体Ⅳ,将按文献制得的中间体Ⅴ与中间体Ⅳ偶合得到目标化合物。结果和结论目标化合物及重要中间体均经IR、1HNMR、MS等确证。OBJECTIVE To synthesize a novel brain-targeted prodrug of 5-fluorouracil(5-Fu) based on thiamine disulfide.METHODS 5-Fu was treated with hexamethyldisilazane and trimethylsilyl chloride to get compound Ⅱ,which was converted to compound Ⅲ by selective acylation with benzyl 6-chloro-6-oxohexanoate.Compound Ⅲ was deprotected by H2 /Pd to afford acid Ⅳ.The compound Ⅳ was coupled with the known compound Ⅴ in the presence of DCC to get title compounds TC.RESULTS and CONCLUSION The chemical structure of the target...

关 键 词：脑靶向 前药 硫胺素二硫化物 5-氟尿嘧啶 合成 

分 类 号：R914[医药卫生—药物化学]