Page 220 - 精细化工2019年第8期

第 36 卷第 8 期 精 细 化 工 Vol.36, No.8
201 9 年 8 月 FINE CHEMICALS Aug. 2019

精细化工中间体
氨基叠氮聚乙二醇的制备

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刘 佳，廉明明，王晓芳，任一冉，欧阳睿博，唐淑坤
（哈尔滨医科大学大庆校区 药学院，黑龙江 大庆 163319）

摘要：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
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特点。产物经 HNMR、 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。
关键词：聚乙二醇；HRMS；氨基叠氮聚乙二醇；液液两相反应；磷脂；精细化工中间体
中图分类号：TQ325.6 文献标识码：A 文章编号：1003-5214 (2019) 08-1708-07

Preparation of Azide Amino Polyethylene Glycol

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LIU Jia, LIAN Ming-ming, WANG Xiao-fang, REN Yi-ran, OUYANG Rui-bo, TANG Shu-kun
（College of Pharmacy, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, China）

Abstract: Diazide polyethylene glycol (N 3-PEG 1500-N 3) was obtained by two-step functional group
transformation using polyethylene glycol 1500 as starting material. The intermediate was reduced by
organic phase and terminated by aqueous phase to achieve unilateral reduction of diazo group. The reaction
selectivity and conversion rate was evaluated by liquid chromatography-mass spectrometry (LC-MS)
(liquid-phase integral area ratio of representative excimer ion peaks in components). The optimum liquid-
liquid two-phase reaction conditions for the unilateral amino azide polyethylene glycol (NH 2-PEG 1500-N 3)
were obtained by single factor test as follows: molar ratio of N 3-PEG 1500-N 3 to triphenylphosphine oxide
1.0∶1.1, mixture solvent of toluene and dichloromethane with a volume ratio of 3∶2 as organic phase,
2 mol/L hydrochloric acid solution as aqueous phase, volume ratio of organic phase to aqueous phase 1∶1,
reaction time 12 hours and reaction temperature 35 ℃. The yield of NH 2-PEG 1500-N 3 was 72% after
column separation and purification, and the selectivity of unilateral reduction of diazo group was 97%. The
results show that NH 2-PEG 1500-N 3 prepared by this method has a characteristics of high purity, simple
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method and tolerance. The product was characterized by HNMR , CNMR, IR and HRMS. Finally,
NH 2-PEG 1500-N 3 was used to synthesize azide-terminated functionalized phospholipid.
Key words: polyethylene glcol 1500; HRMS; amino azide polyethylene glycol; liquid-liquid two phase;
phospholipid; fine chemical intermediates

聚乙二醇（Polyethylene glycol，PEG）是一类 子在生物体内长循环的性质，被广泛应用于医药、
重要的生物相容性寡聚分子，因其具有增加纳米粒 化工等领域 [1-3] 。聚乙二醇及其衍生物在生物医药领

收稿日期：2019-06-03; 定用日期：2019-07-03; DOI: 10.13550/j.jxhg.20190502
基金项目：国家自然科学基金（20156044）；中国博士后面上项目（2014M561369）；黑龙江省自然科学基金项目（QC2015016）；黑
龙江省大学生创新创业项目（201810226061）;哈尔滨医科大学大庆校区校内科研基金（DQXN201705）
作者简介：刘 佳（1989—），女，助教，硕士，E-mail：Liujia_hayidadq@163.com。联系人：唐淑坤（1992—），女，助教，硕士，
E-mail：562187355@163.com。