796873-51-3

Upstream product

• 74808-10-9 O-(2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl)trichloroacetimidate 
• 104707-00-8 methyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-glucopyranoside 
• 796873-38-6 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-β-D-glucopyranose 

Downstream Products

• 122992-59-0 (2,3-di-O-benzyl-β-D-glucopyranosyl)-O-(1→4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 1379585-59-7 (2,3,4-tri-O-benzyl-β-D-glucopyranosyl)-(1->4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 1379585-60-0 (2,3,6-tri-O-benzyl-β-D-glucopyranosyl)-(1->4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 1379585-58-6 (2,3-di-O-benzyl-4,6-O-benzylidene-β-D-glucopyranosyl)-(1->4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 1379585-66-6 (methyl 2,3-di-O-benzyl-β-D-glucopyranosyluronate)-O-(1→4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 1379585-57-5 (4,6-O-benzylidene-β-D-glucopyranosyl)-(1->4)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose 
• 796873-41-1 [6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-β-D-glucopyranosyl] trichloroacetimidate 
• 796873-53-5 methyl 2-acetamido-6-O-acetyl-3-O-benzyl-2-deoxy-4-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyranoside 
• 796873-52-4 1,6-di-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-D-glucopyranose 
• 796873-42-2 methyl 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyranoside 
• 796873-40-0 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-β-D-glucopyranose 
• 796873-43-3 methyl 2-acetamido-3-O-benzyl-2-deoxy-4-O-(β-D-glucopyranosyluronic acid)-α-D-glucopyranoside 

Relevant academic research and scientific papers

Investigating glycol-split-heparin-derived inhibitors of heparanase: A study of synthetic trisaccharides

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose. As expected, in a heparanase inhibition assay, compound 2 is one order of magnitude more potent than 1. Using molecular modeling techniques we have created a 3D model of 1 and 2 that has been validated by NOESY NMR experiments. The pure synthetic oligosaccharides have allowed the first in depth study of the conformation of a glycol-split glucuronic acid. Introducing a glycol-split unit in the structure of 1 increases the conformational flexibility and shortens the distance between the two glucosamine motives, thus promoting interaction with heparanase. However, comparing the relative activities of 2 and roneparstat, we can conclude that the glycol-split motive is not the only determinant of the strong inhibitory effect of roneparstat.

Synthesis of disaccharides derived from heparin and evaluation of effects on endothelial cell growth and on binding of heparin to FGF-2

The disaccharide β-d-GlcA-(1→4)-α-d-GlcNAc-1→OMe and other small nonsulfated oligosaccharides related to heparin/heparan sulfate have been shown to bind to FGF and activated the fibroblast growth factor (FGF) signalling pathway in (F32) cells expressing the FGF receptor. Synthetic routes to β-d-GlcA-(1→4)-α-d-GlcNAc-1→OMe and a glucose analogue β-d-Glc-(1→4)-α-d-GlcNAc-1→OMe are described. The effects of these disaccharides on endothelial cell growth, which is relevant to angiogenesis, were evaluated and it was found they did not mimic the inhibitory effects that were observed for heparin albumin (HA) and that have also been observed by monosaccharide conjugates. They did not alter bovine aortic endothelial cell (BAEC) proliferation, in the presence of FGF-2 in serum free medium or in absence of FGF-2 in serum free and complete medium. Disaccharides (10 μg/mL) reduced by 25-31% the inhibition caused by HA (10 μg/mL) on BAEC growth in serum-free medium but had no effect in complete medium. There was no evidence obtained for the binding of these oligosaccharides to FGF-2 in competition with HA by ELISA.