三尖杉碱吲哚类似物的全合成

Total Synthesis of Indole Analogues of Cephalotaxine

目的 合成三尖杉碱吲哚类似物。方法 以色胺为原料经缩合、环合、水解与脱羧反应得吲哚哌啶酮化合物 ,经Bischler Napieralski反应得烯胺。通过烯胺的溴化与氧化 重排反应得到吲哚氮杂化合物。用溴苄与吲哚氮杂反应在吲哚环上引入苄基保护基 ,经还原、环合反应合成了三尖杉碱吲哚类似物。结果 经 10步反应合成了三尖杉碱吲哚类似物。总收率 14.3%。结论 合成得三尖杉碱吲哚类似物 ,并对反应作了改进 ,使收率提高 ,副产物减少。

Purpose To synthesize indole analogues of cephalotaxine in order to find new anti tumor compound. Methods Two alkylations of diethyl malonate gave the disubstituted malonate,which condensed with tryptamine in presence of potassium carbonate afforded lactame.Bischler Napieralski reaction gave the enamine.After bromination and Duhamel's oxidative rearrangement,azepinone was prepared.The proton was protected by benzyl.Reduction of gave alcohol which underwent intramolecular cyclization in acidic medium leading to the pentacyclic ketone(indole analogues of cephalotaxine). Results Indole analogues of cephalotaxine was synthesized via 10 steps,the overall yield was 14.3%. Conclusions Indole analogues of cephalotaxine was synthesized,the reaction was improved and the yield was increased,the by product was reduced.