甘草次酸-氟尿嘧啶类抗癌复合物的合成及表征  

Synthesis and characterization of glycyrrhetinic acid-fluorouracil anticancer compound

作　　者：高苗苗[1] 木合布力.阿布力孜 徐方野[1] 董长治[2] 热娜.卡斯木[1] 王永波[1] 阿合买提江.吐尔逊 

机构地区：[1]新疆医科大学药学院药物化学有机教研室,乌鲁木齐830011 [2]法国巴黎第七大学分子药物化学研究中心,巴黎法国75205

出　　处：《新疆医科大学学报》2013年第2期156-161,170,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(30960461);新疆医科大学博士后创新基金(2012-2)

摘　　要：目的制备甘草次酸-氟尿嘧啶类复合物——3-羰基-18β-甘草次酸-1,3-二羟甲基-5-氟尿嘧啶(化合物Ⅴ)并进行结构表征。方法对18β-甘草次酸(化合物Ⅰ)的C3-位羟基进行氧化制备3-羰基-18β-甘草次酸(Ⅱ);将抗癌药5-氟尿嘧啶(Ⅲ)与甲醛缩合制成1,3-二羟甲基-5-氟尿嘧啶(Ⅳ);将化合物Ⅱ与Ⅳ在碱性催化系统作用下进行室温缩合反应制得目标化合物Ⅴ;并对结构进行鉴定。结果目标化合物的产率为72%;理化性质与结构鉴定数据表明为目标化合物。结论目标化合物的制备中,缩合反应的条件控制(无水,DCC/DMAP in DMF,室温反应24h)是合成关键。本研究为进一步进行活性测定奠定了基础。Objective To prepare glycyrrhetinic acid-fluorouracil anticancer complex （V） and to characterize the chemical structure. Methods The target compound （V） was prepared within three-step of reaction. At first, 3-carbonyl-1813-glycyrrhetinic acid （ II ） was prepared by the oxidation of C3-OH group in 1813-glycyrrhetinic acid （ I ） ; anticancer drug 5-fluorouracil （ HI ） reacted with formaldehyde to form 1, 3- bis （hydroxymethyl）-5-fluorouracil （IV）; finaly, compounds II and IV were condenced in alkaline catalytic system to obtain the target compound （ V ） ; the chemical structure of these compounds were determined using routin spectrometrical methods. Results The yield of target compound was 72 % ; the chemical structure was elucidated and the physico-chemical properties were described systematically. Conclusion Opti mal control of the reaction conditions such as the anhydride condition and catalytic system （DCC/DMAP in DMF, RT/24 h） were the key points for obtaining target compound. This work may provide an initial base for pharmacological screening of new liver-targeting anticancer agents from glycyrrhetinic acid-fluorouracil complex.

关 键 词：甘草次酸-氟尿嘧啶 复合物 结构表征 

分 类 号：R914[医药卫生—药物化学]