摘要
为了提高抗肿瘤药物喜树碱的靶向作用,设计并合成了一种喜树碱的环磷酸酯前药。以间氯苯乙酮为起始原料,经过缩合、还原反应,制备了1-间氯苯基-1,3-丙二醇（2）,研究了反应温度对缩合反应的影响。将其与对硝基苯二氯磷酸酯反应合成了制备环磷酸酯前药的重要中间体1-间氯苯基-1,3-丙基环磷酸酯（3）,再以10-羟基喜树碱为底物,与中间体3合成了目标化合物喜树碱环磷酸酯前药（4）。探讨了两种催化剂对目标产物喜树碱环磷酸酯前药合成反应的影响,结果表明,叔丁基氯化镁催化效果较好,反应时间缩短到24 h,产物收率42.5%。中间体及产物结构经1H NMR表征。
In order to improve the targeting of antitumor drug camptothecin, a cyclic phosphate prodrug of camptothecin was de-signed and synthesized. 1-m-Chlorophenyl-1 ,3-propanediol（ 2） was prepared from m-chloroacetophenone by condensation reaction of ketoester,reduction reaction. The effects of reaction temperature on the condensation reaction was investigated. The important inter-mediate of cyclic phosphate prodrug, 1-m-chlorophenyl-l ,3-propanediol cyclic phosphate（3） was synthesized from nitrobenzene di- chloro phosphate and compound 2. The title compound, cyclic phosphate prodrug of camptothecin （ 4 ） was synthesized from 10-hy-droxy camptothecin and compound 3. The influence of two kinds of catalysts on the synthesis of the target product was discussed. The results indicated that,the catalytic effect of tert-butylmagnesium chloride was better,the reaction time was shortened to 24 h, with 42. 5% yield. Intermediates and target product were determined by 4H NMR.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2016年第10期1464-1468,共5页
Chemical Research and Application
关键词
喜树碱
环磷酸酯
前药
合成
campothecin
cyclic phosphate
prodrug
synthesis
