以二肽为连接臂的新型聚乙二醇修饰阿霉素的合成  

Synthesis of Novel Polyethylene Glycol Modified Doxorubicins with Dipeptide Linkers

作　　者：宁喜波 周昊 丁振伟 沈鸿雁[1] NING Xi-bo;ZHOU Hao;DING Zhen-wei;SHEN Hong-yan(KeyLaboraory of Structure-based Drug Design and Discovery of Ministry of Edueation, Shenyang Pharmaceutial University, Shenyang 110016, China;School of Pharmacy, He University, Shenyang 110163, China)

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [2]辽宁何氏医学院药学院,辽宁沈阳110163

出　　处：《合成化学》2019年第6期480-484,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21602140);辽宁省科学技术基金资助项目(201602699)

摘　　要：采用Fmoc固相合成策略,以Wang树脂为载体,Fmoc保护的L-氨基酸为原料,EDC/HOBt为缩合剂,合成了8种聚乙二醇修饰的二肽。以HATU/DIPEA为缩合剂,通过酰化反应将修饰后的多肽连接到阿霉素上,合成了一系列新型阿霉素前药,纯度高于90%,收率高于52%,其结构经^1H NMR和MS(ESI)表征。Eight glycol modified dipeptides were synthesized by Fmoc solid-phase synthetic strategy using Wang resin as carrier, Fmoc-protected L-amino acids as raw materials, and EDC/HOBt as the condensing agent. Then eight novel PEG-modified doxorubicin were synthesized by linking the modified polypeptides to doxorubicin via acylation, using HATU/DIPEA as the condensing agent. The purities were higher than 90%, and the yields were higher than 52%. The structures were characterized by ^1H NMR and MS(ESI).

关 键 词：聚乙二醇 多肽 合成 阿霉素 修饰 前药 

分 类 号：O626[理学—有机化学] R914.4[理学—化学]