92955-20-9

Upstream product

• 87326-81-6 methyl 4-O-acetyl-3-O-benzyl-β-L-idopyranuronate 1,2-(methyl orthoacetate) 
• 87327-03-5 methyl (2,4-di-O-acetyl-3-O-benzyl-α-L-idopyranosyl bromide)uronate 
• 93382-47-9 methyl (acetyl 2,4-di-O-acetyl-3-O-benzyl-α,β-L-idopyranoside)uronate 
• 87326-77-0 methyl 3-O-benzyl-L-idopyranosyluronate 
• 87326-79-2 methyl 1,2,4-tri-O-acetyl-3-O-benzyl-β-L-idopyranosyluronate 
• 87326-76-9 methyl 3-O-benzyl-1,2-O-isopropylidene-α-L-idofuranosiduronate 
• 582-52-5 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose 
• 18685-18-2 3-O-benzyl-1,2-5,6-O-diisopropylidene-α-D-glucofuranose 
• 100-39-0 benzyl bromide 
• 22529-61-9 (1R)-1-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro(2,3-d)(1,3)dioxol-5-yl)ethane-1,2-diol 
• 23558-05-6 3-O-benzyl-1,2-O-isopropylidene-1,5-D-xylo-dialdofuranose 
• 262382-45-6 tris(thiophenyl) 3-O-benzyl-1,2-O-isopropylidene-β-L-orthoidofuranuronate 

Downstream Products

• 92955-22-1 methyl 3-O-benzyl-4-O-trichloroacetyl-β-L-idopyranuronate 1,2-(methyl orthoacetate) 
• 1448263-56-6 methyl 3-O-benzyl-4-O-tert-butyldimethylsilyl-β-L-idopyranuronate 1,2-(methyl-orthoacetate) 
• 1448263-52-2 methyl 2-O-acetyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-2-azido-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-yl-methoxy)ethoxy)ethyl)-6-Olevulinoyl-2-deoxy-β-D-glucopyranoside 
• 1448263-58-8 methyl 2-O-acetyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-2-azido-3-O-benzyl-6-O-levulinoyl-2-deoxy-β-D-glucopyranosyl trichloroacetimidate 
• 1448263-59-9 methyl 3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-2-amino-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-β-D-glucopyranoside 
• 1448263-60-2 methyl 2-O-acetyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-2-acetylamido-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-β-D-glucopyranoside 
• 1448263-61-3 methyl 3-O-benzyl-2-O-sulfonato-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-2-sulfonatamido-6-O-sulfonato-β-D-glucopyranoside 
• 1448263-62-4 methyl 2-O-sulfonato-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate(1→4)-2-acetylamido-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-6-O-sulfonato-β-D-glucopyranoside 
• 1448263-63-5 methyl 3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate(1→4)-2-acetylamido-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-β-D-glucopyranoside 
• 1448263-64-6 methyl 2-O-acetyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-3-O-benzyl-1-O-(2-(2-((2S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ethoxy)ethyl)-2-deoxy-2-sulfonatamido-6-O-sulfonato-β-D-glucopyranoside 
• 1448263-57-7 methyl 2-O-acetyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-α-L-idopyranosyluronate-(1→4)-tert-butyldimethylsilyl (2-azido-3-O-benzyl-6-O-levulinoyl-2-deoxy-β-D-glucopyranoside) 
• 114869-96-4 methyl 6-O-acetyl-3-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-4-O-chloroacetyl-α-L-idopyranosyluronate)-α-D-glucopyranoside 

Relevant academic research and scientific papers

Formal synthesis of a disaccharide repeating unit (IdoA-GlcN) of heparin and heparan sulfate

A concise route to access the key disaccharide repeating unit (IdoA-GlcN) of heparan sulfate is described. The synthesis was accomplished by commercially available diacetone α-d-glucose to functional group transformations, which led to the formation of a

TAILORED GLYCOPOLYMERS AS ANTICOAGULANT HEPARIN MIMETICS

The present disclosure provides for methods and compositions comprising a series of synthetic glycopolymers. The disclosure also relates to a kit which is suitable for carrying out the inventive methods.

HEPARAN SULFATE/HEPARIN MIMETICS WITH ANTI-CHEMOKINE AND ANTI-INFLAMMATORY ACTIVITY

The present disclosure provides for methods and compositions comprising a series of synthetic glycopolymers. The disclosure also relates to a kit which is suitable for carrying out the inventive methods.

Tunable heparan sulfate mimetics for modulating chemokine activity

Heparan sulfate (HS) glycosaminoglycans participate in critical biological processes by modulating the activity of a diverse set of protein binding partners. Such proteins include all known members of the chemokine superfamily, which are thought to guide the migration of immune cells through their interactions with HS. Here, we describe an expedient, divergent synthesis to prepare defined HS glycomimetics that recapitulate the overall structure and activity of HS glycosaminoglycans. Our approach uses a core disaccharide precursor to produce a variety of differentially sulfated glycopolymers. We demonstrate that a specific trisulfated mimetic antagonizes the chemotactic activity of the proinflammatory chemokine RANTES with potency similar to that of heparin, without inhibiting serine proteases in the blood coagulation cascade. Our work provides a general strategy for modulating chemokine activity and dissecting the pleiotropic functions of HS/heparin through the presentation of defined sulfation motifs within polymeric scaffolds.

SYNTHESIS OF HEPARIN FRAGMENTS. A CHEMICAL SYNTHESIS OF THE TRISACCHARIDE O-(2-DEOXY-2-SULFAMIDO-3,6-DI-O-SULFO-α-D-GLUCOPYRANOSYL)-(1->4)-O-(2-O-SULFO-α-L-IDOPYRANOSYL-URONIC ACID)-(1->4)-2-DEOXY-2-SULFAMIDO-6-O-SULFO-D-GLUCOPYRANOSE HEPTASODIUM SALT

Known 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose was first converted into methyl 3-O-benzyl-1,2-O-isopropylidene-β-L-idofuranuronate.Acid hydrolysis, followed by acetylation and treatment with titanium tetrabromide, gave methyl (2,4-di-O-acetyl-3-O-benzyl-α-L-idopyranosyl bromide)uronate, which was immediately transformed into methyl 4-O-acetyl-3-O-benzyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).A two-step replacement of the 4-O-acetyl by a 4-O-chloroacetyl group gave the key derivative, crystalline methyl 3-O-benzyl-4-O-chloroacetyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).Condensation of this orthoester with an excess of crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in chlorobenzene in the presence of 2,6-dimethylpyridinium perchlorate gave crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-4-O-chloroacetyl-α-L-idopyranosyluronate)-α-D-glucopyranoside in 40 percent yield.O-Demonochloroacetylation, followed by condensation with known 3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl bromide in dichloromethane in the presence of 2,4,6-trimethylpyridine, silver triflate, and molecular sieve provided benzyl O-(3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl)-(1->4)-O-(methyl 2-O-acetyl-3-O-benzyl-α-L-idopyranosyluronate)-(1->4)-6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in 88 percent yield.O-Deacetylation with sodium hydroxide, followed successively by O-sulfation in N,N-dimethylformamide in the presence of sulfur trioxide-trimethylamine complex, catalytic hydrogenolysis, and N-sulfation in water with the same sulfating agent, gave the heptasodium salt of O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-α-D-glucopyranosyl)-(1->4)-O-(2-O-sulfo-α-L-idopyranosyluronic acid)-(1->4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose.This trisaccharide, which is a fragment of the minimal antithrombin III-binding region in heparin, neither binds to antithrombin III nor induces anti-Xa activity.