抗疟活性化合物─3-[4-(7-氯喹啉-4-基)哌嗪-1-基]丙酸的合成与结构鉴定

Synthesis and structure identification of the anti-malarial agent 3-[4-(7-choloquinolin-4-yl) piperazin-1-yl] propanoic acid

目的:合成哌喹的一种活性代谢物3-[4-(7-氯喹啉-4-基)哌嗪-1-基]丙酸。方法:以哌嗪、4,7-二氯喹啉为原料,采用氨基保护、取代、脱保护、水解等反应合成3-[4-(7-氯喹啉-4-基)哌嗪-1-基]丙酸,并结合硅胶柱层析洗脱分离纯化样品。结果:成功制备了3-[4-(7-氯喹啉-4-基)哌嗪-1-基]丙酸,产率为62.1%,其结构并通过IR,1H-NMR,13C-NMR,HRMS图谱加以确证。结论:本合成方法操作简单,产率高,适用于以4-哌嗪基喹啉为母核的一系列衍生物的合成。

Objective： To synthesize 3-[4-（7-choloquinolin-4-yl） piperazin-1-yl] propanoic acid,an active metabolite of piperaquine.Methods： Piperazine was mono-protected with BOC,then reacted with ethyl 3-bromopropanoiate,subsequently deprotection,and substitution with 4,7-dichloroquinoline,and hydrolysis in consequence,afforded 3-[4-（7-choloquinolin-4-yl） piperazin-1-yl] propanoic acid.The target compound was further isolated and purified by silica gel chromatography.Results： 3-[4-（7-choloquinolin-4-yl） piperazin-1-yl] propanoic acid was synthesized successfully and the yield was 62.1%.The structure was confirmed by IR,1H-NMR,13C-NMR and HRMS.Conclusion： The synthesis method is simple,and the yield of 3-[4-（7-choloquinolin-4-yl） piperazin-1-yl] propanoic acid is high,so that it can be used for the synthesis of derivatives containing 4-piperazinyl quinoline ring.