Synthesis of nucleoside-peptide conjugate with disulfide bond as linker at C-5 of uridine  

以二硫键连接尿嘧啶核苷C-5位肽缀合物的合成(英文)

作　　者：聂菲璘[1] 王晓峰[1] 刘洋[1] 杨振军[1] 张亮仁[1] 张礼和[1] 

机构地区：[1]北京大学天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2008年第3期203-208,共6页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.20332010);the Ministry of Science and Technology of China(Grant No.2005BA711A04,2006AA02Z144).

摘　　要：In order to prepare pyrimidine nucleoside-peptide conjugate concisely, we developed a one-pot synthetic strategy. Started from uridine, 5-S-acetyl-thiomethyl-2＇,3 ＇-di-O-isopropylidene-uridine （4） was synthesized as the key intermediate in four steps. Under acidic condition, compound 4 was deprotected and reacted with PySS-R （8, 12, 15, Py = 2-pyridyl, R = amino acid or peptide） in one pot to form uridine conjugates （9, 13, 2） with disulfide bond as linker.为了方便快捷地制备嘧啶核苷-肽缀合物,我们发展了一种一釜合成的方法。从尿嘧啶核苷出发,经过4步制备了关键中间体5-乙酰巯亚甲基-2′,3′-二-O-异亚丙基尿苷(4)。在酸性条件下,脱除化合物4的乙酰基,同时游离的巯基与PySS-R(8,12,15,Py=2-吡啶基,R=氨基酸或肽)反应形成新的二硫键,即形成了尿苷与氨基酸或肽以二硫键连接的缀合物(9,13,2)。

关 键 词：Nucleoside-peptide conjugate Thiol exchange Disulfide bond formation 

分 类 号：R914[医药卫生—药物化学]