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

Abstract

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.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents

“…To avoid the use of animal-sourced molecules, the total synthesis of the FuCS trisaccharide unit has been accomplished by the groups of Ta muraa nd Nifantiev. [20] In addition, am odular approacht oalibrary of semisynthetic FuCS species has very recently been proposed by the group of Bedini through chemical fucosylation of am icrobial-sourced chondroitin polysaccharide. [21] To the best of our knowledge,a nticoagulant evaluation of FuCS derivatives with ap recise structure has only been reported by Zhao et al, who elucidated that FuCS and its depolymerized fragments selectively inhibited the intrinsic coagulation pathway,a nd an onasaccharide was the minimums tructural unit that retained potent activity.…”

Conformational Analysis of the Oligosaccharides Related to Side Chains of Holothurian Fucosylated Chondroitin Sulfates

“…The synthesis and detailed characterization of compounds 1 – 5 are described in [ 16 ]. For all NMR experiments, D 2 O was used as a solvent (99.98% D, Merck, Darmstadt, Germany).…”

“…These are three disaccharides ( Figure 1 ) and two trisaccharides containing fucose and glucuronic acid residues with a single sulfate group per each fucose residue. The synthesis and detailed characterization of these compounds are described in [ 16 ].…”

Chemical Synthesis of Oligosaccharides Related to the Cell Walls of Plants and Algae

“…In 2014 and 2015, Toshima and co-workers designed a series of type I and type II fucoidan tetrasaccharides with different sulfation patterns. 246,251 An orthogonal deprotection strategy utilizing the common key intermediates 528 and 531 (Scheme 56), carrying three types of protecting groups A recent discovery showed that the fucoidan from the brown seaweed The assembly of both pentasaccharide targets 547 and 548 started with glycosylation between difucopyranoside acceptor 538 and glucuronate donor 539, affording the trisaccharide 540 as a 4:1 α:β-mixture. The pure α-isomer 540 could be isolated after removal of the TBS group.…”