摘要
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).
作者
吕昌仑
苏凯强
李尧
陈海鹪
李春霞
LV Chang-lun;SU Kai-qiang;LI Yao;CHEN Hai-jiao;LI Chun-xia(Key Laboratory of Marine Drugs,Ministry of Education,Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory of Marine Drugs and Bioproducts of Qingdao Pilot National Laboratory for Marine Science and Technology,Qingdao 266237,China)
出处
《中国海洋药物》
CAS
CSCD
2020年第6期1-11,共11页
Chinese Journal of Marine Drugs
基金
国家重大新药创制专项(2018ZX09305004)
山东省重大科技创新工程专项(2018SDKJ0404-2)
国家自然科学基金-山东省联合基金项目(U1606403-1)
山东省自然科学基金项目(ZR2017MH096)资助。
关键词
岩藻糖基化硫酸软骨素
三糖
硫酸化
fucosylated chondroitin sulfate
trisaccharide
sulfation