氨基叠氮聚乙二醇的制备

以聚乙二醇1500为起始原料,经两步官能团转化得到双叠氮基聚乙二醇(N_3-PEG_(1500)-N_3),该中间体经有机相还原、水相终止,实现双叠氮基的单侧还原。反应选择性及转化率经液质联用(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。利用单因素实验,确定氨基叠氮聚乙二醇(NH_2-PEG_(1500)-N_3)最佳液液两相反应条件如下:N_3-PEG_(1500)-N_3与三苯基膦的物质的量比为1.0∶1.1,有机相为V(甲苯)∶V(二氯甲烷)=3∶2的混合溶液,水相为2.0 mol/L盐酸溶液,两相体积比1∶1,35℃下反应12 h,经柱分离提纯得NH_2-PEG-N_3,收率72%,单侧叠氮基还原选择性达97%。实验结果表明,该法制备NH_2-PEG_(1500)-N_3具有纯度高、方法简便等特点。产物经~1HNMR、~(13)CNMR、IR和HRMS进行结构确证。利用NH_2-PEG-N_3实现了叠氮封端功能化磷脂的合成。

Preparation of Azide Amino Polyethylene Glycol

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.