UPS, LHFA, Universite de Toulouse, 118 route de Narbonne, F-31062 Toulouse, France.
Biomacromolecules. 2010 Aug 9;11(8):1921-9. doi: 10.1021/bm100433c.
The (3S)-[(benzyloxycarbonyl)ethyl]-1,4-dioxan-2,5-dione (BED) was prepared in four steps starting from glutamic acid and bromoacetyl bromide. According to X-ray diffraction analysis, the pendant functional group is located in equatorial position and points away from the six-membered ring. The organo-catalyzed ring-opening polymerization of BED was promoted with 4-dimethylaminopyridine (DMAP) and the combination of thiourea TU(Cy) and (-)-sparteine. PolyBED samples of number-average molar mass M(n) up to 36000 and narrow polydispersity (M(w)/M(n) < 1.25) were thereby prepared in a controlled manner under mild conditions (dichloromethane solution, 30 degrees C), as substantiated by size-exclusion chromatography, matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. The pendant functional group does not interfere with the polymerization and BED was even found to be slightly more reactive than lactide. Despite the strongly dissymmetric substitution pattern of the 1,4-dioxan-2,5-dione core, the ensuing polyBED polymers present a random distribution of glycolic-[(benzyloxycarbonyl)ethyl]glycolic (gly glu) units, as supported by a (1)H-(13)C HMBC 2D NMR experiment. The preparation of 1:1 adducts with n-pentanol confirmed that ring-opening of BED occurs almost indifferently on either of the endocyclic ester groups. Poly(alpha-hydroxyacids) featuring pendant carboxylic acids were finally obtained by acetylation of the terminal OH groups followed by hydrogenolysis.
(3S)-[(苄氧羰基)乙基]-1,4-二氧杂戊环-2,5-二酮(BED)由谷氨酸和溴乙酰溴经四步反应制得。根据 X 射线衍射分析,侧基官能团位于赤道位置,指向六元环之外。BED 的开环聚合在 4-二甲氨基吡啶(DMAP)和硫脲 TU(Cy)与(-)-辛可宁的共同作用下得到促进。聚 BED 样品的数均摩尔质量 M(n)高达 36000,且分子量分布较窄(M(w)/M(n) < 1.25),这是在温和条件下(二氯甲烷溶液,30°C)通过控制聚合得到的,这一结果通过凝胶渗透色谱、基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)和核磁共振(NMR)光谱得到证实。侧基官能团不干扰聚合,BED 甚至比丙交酯更具反应活性。尽管 1,4-二氧杂戊环-2,5-二酮核心的取代模式强烈不对称,但所得聚 BED 聚合物呈现出甘醇酸-[(苄氧羰基)乙基]甘醇酸(gly glu)单元的无规分布,这一结果得到了(1)H-(13)C HMBC 2D NMR 实验的支持。与正戊醇的 1:1 加合物的制备证实了 BED 的开环反应几乎在任何一个内脂酯基上都能发生。通过对末端 OH 基团进行乙酰化,然后进行氢解,最终得到了带有侧基羧酸的聚(α-羟基酸)。