具有叠氮化物和炔烃官能团的“点击化学”相容杂双官能聚（乙二醇）的多功能和选择性合成。

Versatile and selective synthesis of "click chemistry" compatible heterobifunctional poly(ethylene glycol)s possessing azide and alkyne functionalities.

机构信息

Department of Materials Engineering, Graduate School of Engineering, and Center for NanoBio Integration, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

出版信息

Bioconjug Chem. 2010 Feb 17;21(2):248-54. doi: 10.1021/bc900253p.

DOI:10.1021/bc900253p

PMID:20078027

Abstract

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 from 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 = NH(2) and SH, Y =Azide and Alkyne) were synthesized with high efficiency and controlled molecular weight.

摘要

建立了一种通过使用 2-（四氢-2H-吡喃-2-基氧基）乙醇作为引发剂开环聚合环氧乙烷来制备α-四氢吡喃氧基-ω-羟基聚（乙二醇）（THP-PEG-OH）的方法，该方法适用于“点击化学”兼容的杂双功能 PEG。然后，通过将羟基与琥珀酸酐进行羧化反应，将 ω-OH 基团官能化至叠氮化物或炔基。THP-PEG-OH 的定量叠氮化反应从衍生物的分子官能度分析中得到证实。虽然 ω-炔基化的转化率适当为 70％，但在羟基用琥珀酸酐进行羧化后，通过离子交换色谱法可以成功地除去未反应的 THP-PEG-OH 部分。然后，在温和的酸性介质中除去α-末端的保护基团 THP，然后再对所得的α-羟基进行两步或三步修饰以得到伯氨基或巯基。因此，高效且可控分子量地合成了“点击化学”兼容的杂双功能 PEG 衍生物（X-PEG-Y；X = NH 2 和 SH，Y = 叠氮化物和炔基）。