Glycosaminoglycans (GAGs) are among the most complex, biologically active polysaccharides in nature. The complexity of GAGs greatly impedes their synthesis, thus complicating the structure-property studies that are so necessary for us to understand the roles of GAGs in natural processes, in pathogen invasion, and to understand how to develop effective interventions, for example, to prevent undesired GAG hijacking by pathogens. Total synthesis of GAG oligomers from monosaccharide building blocks is useful, but incredibly labor-intensive, expensive, and inefficient. In this study, we report a regiospecific synthetic route to two types of designed GAG analogs by chemical modification of commercially available, inexpensive cellulose acetate. Cellulose acetate was first brominated, followed by azide displacement to introduce azides as the GAG amine precursors. The resulting 6-N3 cellulose acetate was then saponified to liberate 6-OH groups. Subsequent oxidation of the liberated primary hydroxyl groups to carboxyl groups was smoothly effected by a TEMPO-catalyzed process. Finally, the azides were reduced to amines using an aqueous process, new to polysaccharide chemistry, employing reduction by dithiothreitol (DTT). Alternatively, another process new to polysaccharide chemistry could be employed to convert most of the azides to acetamido groups (mimicking those present, for example, in native hyaluronic acid) by reduction with thioacetic acid. All the intermediates and products were characterized by 1H NMR, 13C NMR, and FT-IR spectroscopy. This synthetic route provides access to GAG analogs that will be of great interest for exploring structure-property relationships in various biomedical applications.

中文翻译：

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糖胺聚糖类似物的高效合成。

糖胺聚糖（GAG）是自然界中最复杂的，具有生物活性的多糖。GAG的复杂性极大地阻碍了它们的合成，因此使我们了解GAG在自然过程中，病原体入侵中的作用以及了解如何制定有效干预措施（例如预防）的必要的结构性质研究变得非常复杂。病原体不希望的GAG劫持。由单糖结构单元进行GAG低聚物的全合成是有用的，但令人难以置信的是劳动强度大，价格昂贵且效率低下。在这项研究中，我们报告了通过化学修饰可商购的廉价乙酸纤维素制成两种类型的GAG类似物的区域特异性合成途径。首先将乙酸纤维素溴化，然后置换叠氮化物以引入叠氮化物作为GAG胺前体。然后将所得的6-N3乙酸纤维素皂化以释放6-OH基团。TEMPO催化的过程顺利地将游离的伯羟基氧化为羧基。最后，通过二硫苏糖醇（DTT）还原，使用多糖化学新的水合方法将叠氮化物还原为胺。或者，可以采用多糖化学新的另一种方法，通过用硫代乙酸还原，将大多数叠氮化物转化为乙酰氨基基团（模仿例如天然透明质酸中存在的那些）。所有中间体和产物均通过1 H NMR，13 C NMR和FT-IR光谱进行表征。