二棕榈酰磷脂酰胆碱(DPPC)的合成工艺改进  

Improved Synthesis Process of Dipalmitoylphosphatidylcholine(DPPC)

作　　者：吴新宇 刘毓彬[1] 闫闳 林快乐[1] 周伟澄[1] WU Xinyu;LIU Yubin;YAN Hong;LIN Kuaile;ZHOU Weicheng(National Key Lab.of Lead Druggability Research,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,先导物成药性研究全国重点实验室,上海201203

出　　处：《中国医药工业杂志》2024年第8期1085-1088,共4页Chinese Journal of Pharmaceuticals

摘　　要：1,2-二棕榈酰-sn-甘油-3-磷脂酰胆碱(DPPC,1)不仅可作为药用辅料,还可作为外源性肺表面活性剂,治疗新生儿呼吸窘迫综合征(NRDS)。甘油磷脂酰胆碱(GPC,2)在DCM中,在4-二甲氨基吡啶(DMAP)和二环己基碳二亚胺(DCC)的作用下,与棕榈酸(PA,3)反应得DPPC。但发现产生了某一杂质,严重影响产物的纯化。分离、纯化后经MS和1 H NMR确证,该杂质为1,1'-亚甲基双(4-二甲氨基吡啶鎓)双氯化物。把反应溶剂改为乙腈,并将DMAP投料时物质的量比例从3降低至1,目标产物1的收率由33.20%提升至49.18%,纯度99.92%。1,2-Dipalmitoyl-sn-glycero-3-phosphorylcholine(DPPC,1)can be used not only as a pharmaceutical excipient,but also as an exogenous lung surfactant for the treatment of neonatal respiratory distress syndrome(NRDS).Glycerophosphatidylcholine(GPC,2)reacted with palmitic acid(PA,3)in the presence of 4-dimethylaminopyridine(DMAP)and dicyclohexylcarbodiimide(DCC)in DCM to yield 1.But it was found that an impurity was produced,which seriously affected the purification of the product.After isolation and purification,the impurity was confirmed by MS and 1 H NMR to be 1,1'-methylene-bis(4-dimethylaminopyridinium)dichloride.Through replacing reaction solvent to acetonitrile and reducing the feeding molar ratio of DMAP from 3 to 1,the yield of the target product 1 was increased from 33.20%to 49.18%with purity of 99.92%.

关 键 词：1 2-二棕榈酰-sn-甘油-3-磷脂酰胆碱 4-二甲氨基吡啶 合成 杂质 

分 类 号：TQ460.6[化学工程—制药化工] Q545.1[生物学—生物化学]