Synthesis of the Oligosaccharides Related to Branching Sites of Fucosylated Chondroitin Sulfates from Sea Cucumbers

Marine Drugs

Nadezhda E. Ustyuzhanina¹  Polina A. Fomitskaya²  Alexey G. Gerbst¹  Andrey S. Dmitrenok¹  Nikolay E. Nifantiev¹ 

[1] N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow B-334, Russia; E-Mails:;M.V. Lomonosov Moscow State University, Leninskie gory, 119991 Moscow, Russia; E-Mail:

关键词: fucosylated chondroitin sulfate;    oligosaccharides;    synthesis;    glycosylation;    stereoselectivity;    remote participation;    sulfation;   

DOI  :  10.3390/md13020770

来源: mdpi

【 摘 要 】

Natural anionic polysaccharides fucosylated chondroitin sulfates (FCS) from sea cucumbers attract great attention nowadays due to their ability to influence various biological processes, such as blood coagulation, thrombosis, angiogenesis, inflammation, bacterial and viral adhesion. To determine pharmacophore fragments in FCS we have started systematic synthesis of oligosaccharides with well-defined structure related to various fragments of these polysaccharides. In this communication, the synthesis of non-sulfated and selectively O-sulfated di- and trisaccharides structurally related to branching sites of FCS is described. The target compounds are built up of propyl β-d-glucuronic acid residue bearing at O-3 α-l-fucosyl or α-l-fucosyl-(1→3)-α-l-fucosyl substituents. O-Sulfation pattern in the fucose units of the synthetic targets was selected according to the known to date holothurian FCS structures. Stereospecific α-glycoside bond formation was achieved using 2-O-benzyl-3,4-di-O-chloroacetyl-α-l-fucosyl trichloroacetimidate as a donor. Stereochemical outcome of the glycosylation was explained by the remote participation of the chloroacetyl groups with the formation of the stabilized glycosyl cations, which could be attacked by the glycosyl acceptor only from the α-side. The experimental results were in good agreement with the SCF/MP2 calculated energies of such participation. The synthesized oligosaccharides are regarded as model compounds for the determination of a structure-activity relationship in FCS.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.