Versatile and Selective Synthesis of "Click Chemistry" Compatible Heterobifunctional Poly(ethylene glycol)s Possessing Azide and Alkyne Functionalities
Versatile and Selective Synthesis of "Click Chemistry" Compatible Heterobifunctional Poly(ethylene glycol)s Possessing Azide and Alkyne Functionalities
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DOI：
10.1021/bc900253p
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发表时间：
2010-02-01
影响因子：
4.7
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Hiki, Shigehiro;Kataoka, Kazunori
通过使用2-(四氢-2H-吡喃-2-基氧基)乙醇作为引发剂通过环氧乙烷开环聚合制备α-四氢吡喃氧基-omega-羟基聚乙二醇(THP-PEG-OH)，建立了“点击化学”兼容的异双功能PEGS的通用路线，然后通过 将 omega-OH 基团官能化为叠氮基或炔基。 THP-PEG-OH 的定量叠氮化通过衍生物的分子功能性分析得到证实。虽然omega-炔化的转化效率约为70%，但在用琥珀酸酐羧化羟基后，通过离子交换色谱法成功去除了未反应的THP-PEG-OH部分。然后，在弱酸性介质中除去α端的保护基THP，然后将所得α-羟基经过两步或三步修饰为伯氨基或硫醇基团。因此，“点击化学”兼容的异双功能 PEG 衍生物（X-PEG-Y；X = NH2 和 SH，Y = 叠氮化物和炔烃）以高效率和可控的分子量合成。
Versatile route for "click chemistry" compatible heterobifunctional PEGS was established through preparation of alpha-tetrahydropyranyloxy-omega-hydroxyl poly(ethylene glycol) (THP-PEG-OH) via ring-opening polymerization of ethylene oxide using 2-(tetrahydro-2H-pyran-2-yloxy)ethanol as an initiator, followed by the functionalization of omega-OH group to either the azido or alkyne group. Quantitative azidation of THP-PEG-OH was confirmed froth the analysis of molecular functionality of the derivatives. While the conversion efficiency of omega-alkynation was appropriately 70%, the unreacted THP-PEG-OH fraction was successfully removed by ion-exchange chromatography after the carboxylation of the hydroxyl group with succinic anhydride. Then, the protecting group of the alpha-end, THP, was removed in mild acidic media, followed by two- or three-step modification of the resulting alpha-hydroxyl group to primary amino or thiol groups. Consequently, "click chemistry" compatible heterobifunctional PEG derivatives (X-PEG-Y; X = NH2 and SH, Y =Azide and Alkyne) were synthesized with high efficiency and controlled molecular weight.