单分散聚乙二醇的高效合成

Highly efficient synthesis of monodisperse polyethylene glycols

摘要:

以廉价的2~4聚的聚乙二醇为原料，开发了一种基于环硫酸酯的单端延伸法合成单分散聚乙二醇的方法。以苄基作为保护基，重复利用环硫酸酯的亲核开环、水解反应对苄基化聚乙二醇的羟基端进行延伸，以55%～86%的产率得到苄基化的6~16聚的单分散聚乙二醇衍生物，最后通过催化氢化脱去苄基，以95%～99%的产率得到6~16聚的单分散聚乙二醇。中间体及终产物的结构均经NMR和MS确证。反应进程易于监控，反应效率高，无与目标产物的聚合度接近的聚乙二醇杂质，中间体及终产物易于分离纯化。

关键词:聚乙二醇;单分散聚乙二醇;环硫酸酯;合成方法;单端延伸法

Abstract:

A method for the synthesis of monodisperse polyethylene glycols by single chain extension strategy using cheap polyethylene glycols with degree of polymerization of 2 to 4 as raw materials based on macrocyclic sulfates is developed. With benzyl as the protecting group, the hydroxyl end of benzylated polyethylene glycols was extended by repeated nucleophilic ring opening of macrocyclic sulfate and subsequent hydrolysis reaction，and the benzylated monodisperse polyethylene glycol derivatives with degree of polymerization of 6 to 16 were obtained in 55%~86% yield. Finally, monodisperse polyethylene glycols with degree of polymerization of 6 to 16 were obtained in 95%~99% yield through debenzylation by catalytic hydrogenation. The structure of the intermediates and the final products were confirmed by NMR and MS. This method has the following advantages: 1) The reaction process is easy to monitor. 2) The reaction efficiency is high, and no polyethylene glycol impurities with degree of polymerization close to that of the target products were generated, so the intermediates and the final products are easy to be separated and purified.

Key words:polyethylene glycols; monodisperse polyethylene glycols; macrocyclic sulfates; synthetic method; single chain extension strategy