氨基叠氮聚乙二醇的制备

Preparation of Azide Amino Polyethylene Glycol

摘要:

以聚乙二醇1500为起始原料，经两步官能团转化得到同端基双叠氮化聚乙二醇（N3-PEG1500-N3），该中间体经有机相还原、水相终止策略，实现了双叠氮基的单侧还原。反应选择性及转化率经液质联用，及组分中代表性准分子离子峰的液相积分面积比例进行评价。利用单因素试验，确定异端基氨基叠氮聚乙二醇（NH2-PEG1500-N3）最佳液液两相反应条件如下：N3-PEG1500-N3与三苯基氧膦的摩尔比为1：1.1，有机相为甲苯-二氯甲烷混合溶剂（体积比3：2），水相为2 mol/L盐酸溶液，两相比例1：1，35 oC下反应12 h，经柱分离提纯得NH2-PEG-N3收率72%，单侧叠氮基还原选择性达97%。实验结果表明该方法制备NH2-PEG-N3，具有纯度高、方法简便、耐受等特点。产物经1H-NMR和HRMS进行结构表征。最后应用该异端基聚乙二醇，实现了叠氮封端功能化磷脂的合成。

Abstract:

Polyethylene glycol 1500 was used as raw material to synthesize bisazide polyethylene glycol (N3-PEG-N3) intermediate by two-step functional group transformation. One side of the N3-PEG-N3 was reduced by organic phase and terminated by aqueous phase to achieve unilateral reduction of azide. Reaction selectivity was evaluated by liquid chromatography-mass spectrometry (LC-MS) and the content of excimer ion peaks of each component. The reduction rate of azide group on one side reached 97%. The optimum liquid-liquid two phase reaction conditions of amino azide polyethylene glycol (NH2-PEG1500-N3) were determined by single factor experiments: the molar ratio of bisazide polyethylene glycol to tri-phenylphosphine oxide was 1:1.1, the organic phase was toluene and dichloromethane as mixed solvent (3:2), aqueous phase was 2 mol/L hydrochloric acid solution, and the ratio of the two phases was 1:1, reaction at 35 oC for 12 hours, and then NH2-PEG-N3 was purified by column separation, yield is 72%. The results show that this method is simple and high purity. The products were characterized via 1H-NMR and HRMS. Finally, the hetero-polyethylene glycol was used to synthesize azide-terminated functional phos-pholipids.