Synthesis and Application of pH-Sensitive Linkers in Amphiphilic Block Copolymer

doi:10.6023/cjoc201403029

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (9): 1806-1815.DOI: 10.6023/cjoc201403029 Previous Articles Next Articles

酸敏感连接单元的合成及其在两亲性嵌段共聚物中的应用

朱方霞^a, 庄园^a,b, 黎庆^a,b, 杨晴来^a, 伍新燕^b, 邵志峰^a,c, 龚兵^d,e, 沈玉梅^a

a 上海交通大学系统生物医学研究院, bio-Id 研究中心, 系统生物医学教育部重点实验室, 上海 200240;
b 华东理工大学化学与分子工程学院, 精细化工研究所, 上海 200237;
c 上海交通大学生物医学工程学院, bio-Id 研究中心, 上海 200240;
d 北京师范大学化学学院, 北京 100875;
e 布法罗纽约州立大学化学系, 纽约14260 美国

收稿日期:2014-03-12 修回日期:2014-04-28 发布日期:2014-05-07
通讯作者: 龚兵, 沈玉梅 E-mail:yumeishen@sjtu.edu.cn; bgong@buffalo.edu
基金资助:
国家自然科学基金(Nos. 81071250, 91227109)和新药创制重大专项(No. 2011ZX09501-001-05)资助项目.

Synthesis and Application of pH-Sensitive Linkers in Amphiphilic Block Copolymer

Zhu Fangxia^a, Zhuang Yuan^a,b, Li Qing^a,b, Yang Qinglai^a, Wu Xinyan^b, Shao Zhifen^a,c, Gong Bin^d,e, Shen Yumei^a

a Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine and Bio-ID Center, Shanghai Jiao Tong University, Shanghai 200240;
b Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237;
c School of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai 200240;
d College of Chemistry, Beijing Normal University, Beijing 100875;
e Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, USA

Received:2014-03-12 Revised:2014-04-28 Published:2014-05-07
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 81071250, 91227109), ant the Major Projects in National Science and Technology, “Creation of Major New Drugs” (No. 2011ZX09501-001-05).

A series of acid cleavable linkers based on tetrahydropyran/tetrahydrofuran (THP/THF) ether were synthesized, in which both of the two terminals are active group which is easy to react with other compounds. The structures for these linkers 1a and 1b were confirmed by ¹H NMR, ¹³C NMR, HRMS, and IR. Diblock cooligomerModel compound containing THP linkage was synthesized. Furthermore a pH-responsive amphiphilic diblock copolymer containing tetrahydrofuran (THF) linkage in which hydrophilic segment was poly(ethylene glycol) (PEG) and hydrophobic segment was hydrophobic polylactic acid (PLA) was synthesized and characterized by ¹H NMR, IR and gel permeation chromatography (GPC). The size, stability and critical micelle concentration (CMC) of diblock copolymer micelle were also evaluated. The preliminary experimental results show that the acid sensitive amphiphilic diblock copolymer micelle is a potential alternative for future drug delivery.

Key words: THP/THF acid cleavable linker, amphiphilic diblock copolymer, self-assembled micelle

Cite this article

Zhu Fangxia, Zhuang Yuan, Li Qing, Yang Qinglai, Wu Xinyan, Shao Zhifen, Gong Bin, Shen Yumei. Synthesis and Application of pH-Sensitive Linkers in Amphiphilic Block Copolymer[J]. Chin. J. Org. Chem., 2014, 34(9): 1806-1815.

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酸敏感连接单元的合成及其在两亲性嵌段共聚物中的应用

Synthesis and Application of pH-Sensitive Linkers in Amphiphilic Block Copolymer

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