双短链聚乙二醇单甲醚修饰的雷帕霉素水溶性前药的合成

Synthesis of Rapamycin's Water Soluble Prodrugs Modificated with Double Short Chain Methoxypolyethylene Glycols

以Boc保护的谷氨酸和聚乙二醇500单甲醚为原料,经4步反应合成了具有良好水溶性的双短链聚乙二醇结构修饰的雷帕霉素前药(1),其结构经~1H NMR确证。初步的研究结果表明:1具有良好的水溶性,在小鼠体内能够释放出雷帕霉素。

A water soluble prodrug（1） of rapamycin with modification of double short chain methoxypolyethylene glycols was designed and synthesized through four steps of reactions using N-（tert-butoxycarbonyl）-L-glutamic acid and MPEG of 500 dalton as starting materials. The structure was confirmed by^1H NMR. The preliminary study showed that 1 had good water solubility,and rapamycin was metabolized from 1 in mice.