1种岩藻糖基化硫酸软骨素三糖的合成

Synthesis of fucosylated chondroitin sulfate trisaccharide

目的通过化学合成的方法制备结构确证的FCS寡糖以研究其作用机制及构效关系。方法基于天然海参中FCS结构,从单糖砌块开始,通过线性合成策略进行FCS三糖化合物的合成。结果从功能化的单糖砌块开始,以12步反应23%的总收率制备了岩藻糖3,4位硫酸化的FCS三糖重复单元β-D-GalNAc(4,6-diS)(1-4)[α-L-Fuc(3,4-diS)(1-3)]-β-D-GlcA-OMP。结论在合成中,建立了选择性O-硫酸化以及立体选择性糖基化的保护基策略,同时以高产率实现了各砌块间的偶联,为FCS类寡糖的合成研究提供了参考。化合物结构经1H NMR,13C NMR和HR-MS(ESI)表征。

Objective To prepare structure-confirmed FCS oligosaccharides by chemical synthesis to study its mechanism of action and structure-activity relationship.Methods Based on the structure of FCS in natural sea cucumbers,starting from monosaccharide blocks,the synthesis of FCS trisaccharide compounds was carried out by a linear synthesis strategy.Results We synthesized an FCS trisaccharide repeat unit with 3,4-disulfo fucosyl residue,β-D-GalNAc(4,6-diS)(1-4)[α-L-Fuc(3,4-diS)(1-3)]-β-D-GlcA-OMP,in a total yield of 23%through 12 steps reaction,starting from the functionalized monosaccharide building blocks.Conclusion In the synthesis,the protective group strategy for selective O-sulfation and stereoselective glycosylation was established,and the coupling between the blocks was achieved in high yield.Our research work provided a reference for the synthesis of FCS-related oligosaccharides.The structures were characterized by 1 H NMR,13 C NMR and HR-MS(ESI).