2-(1-羟基)乙基二氢卟吩f及其醚衍生物的合成和肿瘤光生物活性

Synthesis and TumorPhotobiological Activities of 2-(1-Hydroxyl)ethyl chlorin f and Its Ether Derivatives

以蚕沙叶绿素稳定降解产物二氢卟吩f(2 )为关键中间体 ,设计合成了 2 (1 羟基 )乙基二氢卟吩f(3a)及其醚类衍生物 3b～ 3d、4b～ 4d ,其中 ,3a、3c、3d、4c、4d为新化合物 ,用UV、IR、1H NMR和FAB -MS确证了它们的结构。同时测定了目标物 3a、4b～ 4d对小鼠肉瘤 180移植瘤的光动力治疗作用 ,结果显示 :2 (1 羟基 )乙基二氢卟吩f醚衍生物 4b～ 4d对小鼠肉瘤 180移植瘤的光动力治疗效果均优于参比药物血卟啉衍生物 (HpD) ,且随醚链增长而增强 ,而 3a却无效 。

hydroxyl)ethyl chlorin f(3a)and its six ether derivatives(3b～3d、4b～4d)were designed and synthesized via HBr addition of 2 vinyl of chlorin f(2)which was prepared through acidic and alkaline oxidative degradation using silkworm excrement crude chlorophyll extracts as the starting material followed by H 2O,MeOH, n C 3H 7OH, n C 5H 11 nucleophilic substitution and hydrolysis.3a,3c,3d,4c and 4d were new compounds.Their structures were confirmed by UV,IR, 1H NMR and FAB MS.The photodynamic effects of the target compounds(3a,4b,4c and 4d)on sarcoma 180 transplanted in mice were determined.The results of preliminary experiment showed that 4b,4c and 4d had more efficacious photochemotherapeutic potency than that of HpD,and 4d was the best among them,but 3a had no photochemotherapeutic potency.It is suggested that the photochemotherapeutic potency of 2 (1 hydroxyl)ethyl chlorin f ether derivatives on sarcoma 180 transplanted in mice enhance as their chain length increase and further studies on their structure action relationship(SAR)seem to be of importance as well.