二棕榈酰磷脂酰胆碱(DPPC)的合成工艺改进

Improved Synthesis Process of Dipalmitoylphosphatidylcholine(DPPC)

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%.