由喜树碱制备盐酸拓扑替康

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℃)。

Synthesis of Topotecan Hydrochloride from Camptothecin

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 ℃.