76946-04-8

Upstream product

• 162118-38-9 (3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-ol 
• 169532-17-6 ethyl 2,3,4-tri-O-benzyl-1-thio-α/β-L-fucopyranoside 
• 116514-50-2 ethyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside 
• 7404-35-5 1,2,3,4-tetra-O-acetyl-L-fucopyranose 
• 73-34-7 6-deoxy-L-galactose 
• 167612-35-3 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside 
• 187233-24-5 phenyl 6-deoxy-1-thio-β-L-galactopyranoside 
• 167612-34-2 phenyl 6-deoxy-2,3,4-tri-O-acetyl-1-thio-β-L-galactopyranoside 
• 131545-02-3 ethyl 2,3,4-tri-O-benzyl-1-thio-α-L-fucopyranoside 

Downstream Products

• 252896-24-5 Acetic acid (2R,3S,4S,5R,6R)-3,5-diacetoxy-2-acetoxymethyl-6-[(2R,3S,4R)-2-benzyloxymethyl-3-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yloxy]-tetrahydro-pyran-4-yl ester 
• 322761-78-4 O-3-O-[(1S)-1-cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-2,4,6-tris-O-(phenylmethyl)-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-2,3,4-tris-O-(phenylmethyl)-α-L-galactopyranosyl-(1->4)]-1,5-anhydro-2-deoxy-D-arabino-hexitol 
• 203794-75-6 9-[(2R,4aR,6R,7R,8R,8aS)-7-Allyloxycarbonylamino-2-phenyl-8-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy]-nonanoic acid methyl ester 
• 860812-51-7 3-[(N-benzyloxycarbonyl)amino]propyl 2,3,4-tri-O-benzyl-β-L-fucospyranoside 
• 1250831-24-3 O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→2)-O-(6-O-pivaloyl-3,4-isopropylidene-β-D-galactopyranosyl)-(1→4)-2,3:5,6-di-O-isopropylidene-D-glucose dimethyl acetal 
• 15839-70-0 guanosine 5’-diphospho-L-fucose 
• 173683-13-1 (2R,4S,5R,6R)-4-Acetoxy-5-acetylamino-6-((1S,2R)-1,2,3-triacetoxy-propyl)-2-[6-((2R,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-hexyloxy]-tetrahydro-pyran-2-carboxylic acid methyl ester 
• 178872-62-3 Sulfuric acid mono-[6-((2R,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-hexyl] ester 
• 252896-26-7 2-{2-[2-benzyloxymethyl-3-(3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yloxy]-3,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-4-yloxy}-3-cyclohexyl-propionic acid benzyl ester 
• 252896-25-6 (2R,3R,4S,5R,6R)-2-[(2R,3S,4R)-2-Benzyloxymethyl-3-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yloxy]-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol 
• 203794-79-0 9-[(2R,3R,4R,5S,6R)-6-Benzyloxymethyl-3-(3,4-dimethoxy-benzoylamino)-5-hydroxy-4-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxy]-nonanoic acid methyl ester 
• 203794-76-7 9-[(2R,3R,4R,5S,6R)-3-Allyloxycarbonylamino-6-benzyloxymethyl-5-hydroxy-4-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxy]-nonanoic acid methyl ester 
• 203794-77-8 9-[(2R,3R,4R,5S,6R)-3-Amino-6-benzyloxymethyl-5-hydroxy-4-((2S,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxy]-nonanoic acid methyl ester 

Relevant academic research and scientific papers

PROCESS FOR PREPARING AN E-SELECTIN INHIBITOR INTERMEDIATE

A process is provided for the synthesis of an intermediate of Formula 15 which is useful in the synthesis of E-selectin inhibitors. Also provided are useful intermediates obtained from the process.

Synthesis of blood group A and B (type 2) tetrasaccharides. A strategy with fucosylation at the last stage

The traditionally used strategy for the synthesis of blood group A and B tetrasaccharides includes 2′-O-fucosylation of lactosamine followed by insertion of an α1-3 linked N-acetylgalactosamine or a galactose moiety. Here, we report the synthesis of 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides via an alternative sequence, i.e. α-galactosaminylation (or α-galactosylation) followed by α-fucosylation. This strategy allows us to synthesize fucose-free trisaccharides GalNAcα1-3Galβ1-4GlcNAc and Galα1-3Galβ1-4GlcNAc, which are promising targets for immunotherapy utilising human natural antibodies against the trisaccharides. The key stage in this scheme was the selective chloroacetylation of the 2′-OH group of βGal in the intermediate trisaccharides having the second (3-OH) unprotected group.The protocol is suitable for multigram syntheses and its further scaling up.

Kilogram scale chemical synthesis of 2′-fucosyllactose

A scalable synthetic procedure to high quality 2′-fucosyllactose, the most abundant oligosaccharide in human breast milk, has been designed and validated in kilogram scale. The synthetic route has been developed to suit industrial environment and contains

Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines

Methods are provided for using a compound to treat, for example, endothelial dysfunction including vascular abnormalities. More specifically, methods are described for using an oligosaccharide compound or glycomimetic compound wherein a cyclohexane derivative is incorporated in either.

Synthesis and biological evaluation of E-selectin antagonists that present different carbohydrate ligands in a multivalent format

The synthesis of the first polylysine conjugates that present different carbohydrate ligands in a multivalent format is reported. Glycopolymers 3c and 3d have been prepared with a highly predictable composition as indicated by 1H NMR. They func

An easy access to halide ion-catalytic alpha-glycosylation using carbon tetrabromide and triphenylphosphine as multifunctional reagents.

The reaction of a 2-O-benzyl-1-hydroxy sugar with CBr4 and Ph3P generates a glycosyl bromide in situ, which is coupled with an acceptor alcohol in the presence of N,N-tetramethylurea to afford an alpha-glycosyl product virtually quantitatively. In a proposed pathway, the reagent combination plays multiple roles such as the generation of a glycosyl donor, the activation of glycosylation, and the dehydration of the reaction system. These roles allow a simple alpha-glycosylation to be performed without special attention to dehydration. Various alpha-glycosyl (D-gluco-, D-galacto- and L-fuco-) products including glycosyl glycerols and cholesterols have been prepared with this method.

Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly improved E-selectin inhibition

The synthesis of the highly potent E-selectin inhibitor 5 is described. Sialyl Lewis X mimic 5 was rationally designed by combining two previously disclosed beneficial sLex modifications in a single molecule. The compound was found to be 30-fold more potent than sLex in a static, cell-free equilibrium assay. Furthermore, compound 5 was highly active (IC50 = 10 μM) in a dynamic non-equilibrium assay in which sLex did not inhibit neutrophil rolling at up to 1000 μM.

Potent E-selectin antagonists

In the search for drugs that could control excessive leukocyte extravasation, we now report on modifications of the already known potent E-selectin antagonist 3 containing a cyclohexyllactic acid residue and a glucal-derived building block. Thus, we describe the synthesis and biological evaluation of a series of derivatives 6 with modified glucal-derived moieties (CH2NR1R2 instead of CH2OH in 3) to explore a hypothetical potential complementary interaction with E-selectin. However, similar activity profiles of most derivatives 6 and compound 3 do not support such an interaction, but rather indicate topological-structure changes of 6 (and 3) in the orientation of the neighboring fucose and galactose due to intramolecular steric interactions. The most potent E-selectin antagonist 6v showed >50-fold improved E-selectin inhibition compared to the weak selectin ligand sialyl Lewis' (sLex, 1: IC50 = 1000-1500μM), but only a 2-fold improvement compared to 3. Compound 6x was tested in vivo in a murine model of acute inflammation and found to be as potent as 3 (ED50 = 15 mg/kg).

Synthesis, NMR and conformational studies of fucoidan fragments 1: 1 desulfated 2,3-and 3,4-branched trisaccharide fragments and constituting disaccharides

Two fucotriosides with vicinal disubstitution α-L-Fuc-(1→2)[α-L-Fuc-(1→3)]α-L-Fuc-OPr (1) and α-L-Fuc-(1→3)[α-L-Fuc-(1→4)]α-L-Fuc-OPr (2), which are related to fragments of natural polysaccharides fucoidans, have been synthesized together with constituent disaccharides 3-5. Spectral and conformational properties of tri-and disaccharides have been investigated by 1H, 12C and NOE NMR spectroscopy.

Synthesis and Biological Evaluation of a Potent E-Selectin Antagonist

An early step of the inflammatory response - the rolling of leukocytes on activated endothelial cells - is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialyl Lewisx (sLex) 1 is a ligand for E-, P-, and L-selectin and, therefore, serves as a lead structure to develop analogues which allow the control of acute and chronic inflammation. Here we describe the efficient synthesis (10 linear steps) of the potent sLex mimetic 2. Compared to sLex, compound 2 showed a 30-fold improved affinity in a static, cell-free E-selectin-ligand binding assay (IC50 = 36 μM). These data were confirmed by a marked inhibition in an in vitro cell-cell rolling assay which simulates in vivo conditions (IC50 ca. 40 μM). The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED50 ca. 15 mg/kg).