Facile Synthesis of Acid-Labile Polymers with Pendent Ortho Esters
Facile Synthesis of Acid-Labile Polymers with Pendent Ortho Esters
复制标题
具有悬垂原酸酯的酸不稳定聚合物的简便合成
DOI：
10.1021/bm201410c
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发表时间：
2012-01-01
影响因子：
6.2
通讯作者：
Li, Zi-Chen
中科院分区：
文献类型：
--
作者：
Cheng, Jing;Ji, Ran;Li, Zi-Chen
本工作提出了一种制备具有侧链环状原酸酯的酸不稳定和生物相容性聚合物的简便方法，该方法基于环状烯酮缩醛（CKA）与羟基之间的有效且温和的反应。以环状乙烯基缩醛为原料，通过双键催化异构化反应合成了3种CKAs：2-亚乙基-1，3-二氧六环（EDO）、2-亚乙基-1，3-二氧戊环（EDL）和2-亚乙基-4-甲基-1，3-二氧戊环（EMD）。使用痕量对甲苯磺酸作为催化剂，检查CKAs与不同醇和二醇的反应。对于单羟基醇，通过向CKAs简单地添加羟基形成环状原酸酯，其中乙醇显示出比异丙醇大得多的反应性。当1，2-或1，3-二醇与CKAs反应时，除了简单的加成产物外，还观察到了异构化的环状原酸酯。生物相容性的多元醇，即聚（2-羟乙基丙烯酸酯）（PHEA）和聚（乙烯醇）（PVA），然后与CKAs改性，和侧的原酸酯的取代度可以很容易地通过改变进料比进行调节。小分子原酸酯和CKA改性的聚合物都表现出pH依赖性水解曲线，这也取决于原酸酯的化学结构以及聚合物的疏水性。
This work presents a facile approach for preparation of acid-labile and biocompatible polymers with pendent cyclic ortho esters, which is based on the efficient and mild reactions between cyclic ketene acetal (CKA) and hydroxyl groups. Three CKAs, 2-ethylidene-1,3-dioxane (EDO), 2-ethylidene-1,3-dioxolane (EDL), and 2-ethylidene-4- methyl-1,3-dioxolane (EMD) were prepared from the corresponding cyclic vinyl acetals by catalytic isomerization of the double bond. The reaction of CKAs with different alcohols and diols was examined using trace of p-toluenesulfonic acid as a catalyst. For the monohydroxyl alcohols, cyclic ortho esters were formed by simple addition of the hydroxyl group toward CKAs with ethanol showing a much greater reactivity than iso-propanol. When 1,2- or 1,3-diols were used to react with the CKAs, we observed the isomerized cyclic ortho esters besides the simple addition products. Biocompatible polyols, that is, poly(2-hydroxyethyl acrylate) (PHEA) and poly(vinyl alcohol) (PVA) were then modified with CKAs, and the degree of substitution of the pendent ortho esters can be easily tuned by changing feed ratio. Both the small molecule ortho esters and the CKA-modified polymers demonstrate the pH-dependent hydrolysis profiles, which depend also on the chemical structure of the ortho esters as well as the polymer hydrophobicity.