由喜树碱制备盐酸拓扑替康  

Synthesis of Topotecan Hydrochloride from Camptothecin

作　　者：王升[1] 白云峰[1] 李斌[1] 贾梦秋[1] 徐春艳[1] 薛传薪[1] 

机构地区：[1]北京化工大学理学院,北京100029

出　　处：《精细化工》2004年第12期927-929,937,共4页Fine Chemicals

摘　　要：以喜树碱(CPT)为原料,采用氧化、光化及Mannich3步反应的路线合成了盐酸拓扑替康(TPT),通过对反应条件的优化,确定氧化反应最佳条件为:反应时间4h、反应温度75℃、0 01mol喜树碱,w(H2O2)=30%的双氧水48mL、乙酸350mL;光化反应条件:V(1,4 二氧六环)∶V(乙腈)∶V(H2O)=5∶4∶1为溶剂,浓硫酸为催化剂;Mannich反应条件:n(羟基喜树碱)∶n(甲醛)∶n(二甲胺水溶液)=1∶9 3∶5 5,反应温度45℃。盐酸拓扑替康总收率35 9%(文献值[4]29%)、w(TPT)=98 50%、熔点213～217℃(文献值[6]213～218℃)。Topotecan hydrochloride (TPT) was synthesized from camptothecin (CPT)through oxidation,photochemical reaction and Mannich reaction.The optimized reaction conditions were as follows.For the oxidation reaction,the reaction time was 4 h,the reaction temperature 75 ℃,amount of H_2O_2 48 mL〔w(H_2O_2)=30%〕,and amount of CH_3COOH 350 mL(based on 0.01 mol CPT).In photochemical reaction,the solvent was composed of V(1,4-dioxane)∶V(acetonitrile)∶V(H_2O_2)=5∶4∶1,and 98% H_2SO_4 was used as catalyst.In Mannich reaction,n(hydroxycamptothecin)∶n(CH_2O)∶n(dimethylamine)=1∶9.3∶5.5,and the reaction temperature was 45 ℃.The total yield of TPT is 35.9% with 98.50% purity and m.p.213～217 ℃.

关 键 词：盐酸拓扑替康 喜树碱 光化反应 MANNICH反应 

分 类 号：R979.1[医药卫生—药品]