Synthesis and Characterization of Multi-Reducing-End Polysaccharides
Synthesis and Characterization of Multi-Reducing-End Polysaccharides
复制标题
多还原端多糖的合成与表征
DOI：
10.1021/acs.biomac.3c00104
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发表时间：
2023-06-01
影响因子：
6.2
通讯作者：
Edgar，Kevin J.
中科院分区：
文献类型：
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作者：
Zhai，Zhenghao;Zhou，Yang;Edgar，Kevin J.
对多糖科学家来说，位点特异性修饰是一个巨大的挑战。多糖链的化学和区域选择性修饰可以提供许多有用的天然基材料，并有助于阐明多糖衍生物的基本结构-性质关系。多糖的半缩醛还原端与其开环醛形式处于平衡状态，使其成为多糖分子上最独特的活性位点，非常适合区域选择性修饰，如亚胺的形成。然而，所有的天然多糖，无论是否支链，每条链上都只有一个还原端，这意味着只能添加一个醛反应取代基。我们介绍了一种将多糖选择性功能化的新方法，将其作为有用物质的载体，在每个多糖分子上附加多个还原端。在这里，我们减少了使用酰胺形成的方法。单糖上的氨基，如葡萄糖胺或半乳糖胺，可以与多糖的羧基发生反应，无论是天然糖醛酸，如海藻酸盐，还是含有羧基取代基的衍生物，如羧甲基纤维素（CMC）或羧甲基葡聚糖（CMD）。偶联剂4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基酰氯胺（DMTMM）辅助酰胺的形成。通过这种方法将单糖的C2胺与多糖连接，可以得到一类具有多个还原端的多糖衍生物。我们把这类衍生物称为多还原端多糖（MREPs）。这一新的衍生物家族为设计具有许多潜在应用的多糖基材料创造了潜力，包括水凝胶，嵌段共聚物，前药以及其他衍生物的反应中间体。
Site-specific modification is a great challenge for polysaccharide scientists. Chemo- and regioselective modification of polysaccharide chains can provide many useful natural-based materials and help us illuminate fundamental structure–property relationships of polysaccharide derivatives. The hemiacetal reducing end of a polysaccharide is in equilibrium with its ring-opened aldehyde form, making it the most uniquely reactive site on the polysaccharide molecule, ideal for regioselective decoration such as imine formation. However, all natural polysaccharides, whether they are branched or not, have only one reducing end per chain, which means that only one aldehyde-reactive substituent can be added. We introduce a new approach to selective functionalization of polysaccharides as an entrée to useful materials, appending multiple reducing ends to each polysaccharide molecule. Herein, we reduce the approach to practice using amide formation. Amine groups on monosaccharides such as glucosamine or galactosamine can react with carboxyl groups of polysaccharides, whether natural uronic acids like alginates, or derivatives with carboxyl-containing substituents such as carboxymethyl cellulose (CMC) or carboxymethyl dextran (CMD). Amide formation is assisted using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM). By linking the C2 amines of monosaccharides to polysaccharides in this way, a new class of polysaccharide derivatives possessing many reducing ends can be obtained. We refer to this class of derivatives as multi-reducing-end polysaccharides (MREPs). This new family of derivatives creates the potential for designing polysaccharide-based materials with many potential applications, including in hydrogels, block copolymers, prodrugs, and as reactive intermediates for other derivatives.