67109-74-4

Usage

Uses

Used in Pharmaceutical Industry:
5-[(Acetyloxy)Methyl]-3a,6,7,7a-tetrahydro-2-Methyl-(3aR,5R,6S,7R,7aR)-5H-Pyrano[3,2-d]thiazole-6,7-diol Diacetate (Ester) is used as an intermediate in the synthesis of Hexosaminidase inhibitor derivatives. These derivatives are considered new drug candidates for the therapy of osteoporosis, a condition characterized by weakened bones and an increased risk of fractures. 5-[(Acetyloxy)Methyl]-3a,6,7,7a-tetrahydro-2-Methyl-(3aR,5R,6S,7R,7aR)-5H-Pyrano[3,2-d]thiazole-6,7-diol Diacetate (Ester)'s unique structure and functional groups contribute to the development of effective inhibitors that can target and modulate the activity of Hexosaminidase enzymes, potentially leading to improved bone health and reduced osteoporosis-related complications.

Upstream product

• 3006-60-8 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranose 
• 1078691-95-8 (+)-D-glucosamine hydrochloride 
• 51471-40-0 6-(hydroxymethyl)-3-[4-methoxybenzylideneamino]tetrahydropyran-2,4,5-triol 
• 5432-46-2 1,3,4,6-tetra-O-acetyl-D-glucosamine hydrochloride 

Downstream Products

• 179030-22-9 (3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol 
• 343925-61-1 (2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-mercaptotetrahydro-2H-pyran-3,4-diyl diacetate 
• 1332868-18-4 C₁₅H₁₉NO₄S 
• 479255-65-7 cyclohexyl 2-acetamido-2-deoxy-1-thio-3,4,6-tri-O-acetyl-α-D-glucopyranoside 

Relevant academic research and scientific papers

Synthesis of NAG-thiazoline-derived inhibitors for β-N-acetyl-d-hexosaminidases

Abstract β-N-Acetyl-d-hexosaminidases are responsible for the metabolism of glycoconjugates in diverse physiological processes that are important targets for medicine and pesticide development. Fourteen new NAG-thiazoline derivatives were synthesized by cyclization and click reaction using d-glucosamine hydrochloride as the starting material. All the compounds created were characterized by NMR and HRMS spectra. A preliminary bioassay, using four enzymes from two β-N-acetyl-d-hexosaminidase families, showed that most of the compounds synthesized exhibit selective inhibition of GH84 β-N-acetyl-d-hexosaminidase. Among the compounds tested, compounds 5a (IC50=12.6 μM, hOGA) and 5e (IC50=12.5 μM, OfOGA) proved to be a highly selective and potent inhibitor.

Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies

By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using 1H saturation transfer difference (STD) effects and transferred 1H,1H-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides β-d-Galp-(1→4) -β-d-GlcpNAc-OMe and β-d-GlcpNAc-(1→4)-β-d-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/π-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N′-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on 1H NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process. The Royal Society of Chemistry 2012.

SELECTIVE GLYCOSIDASE INHIBITORS, METHODS OF MAKING INHIBITORS, AND USES THEREOF

The invention comprises compounds for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions containing the compounds or prodrugs of the compounds. The invention also comprises animal models and methods of making the animal models for studying diseases and disorders related to deficiency or overexpression of O-GIcNAcase, accumulation or deficiency of O-GIcNAc, and treatment of such diseases and disorders. The invention also comprises methods of treating such diseases and disorders. The invention also comprises methods of making the compounds, and methods of making selective glycosidase inhibitors

Iminocyclitol inhibitors of hexoaminidase and glycosidase

Designed iminocylitols that have potent inhibition activity with respect to hexominidases and glycosides are disclosed.

Shortcut to mycothiol analogues

(equation presented) The synthesis of a simplified thioglycosidic analogue (2) of mycothiol (1) is described. Evaluation of 2 against mycothiol S-conjugate amidase from Mycobacterium tuberculosis reveals good specific activity (7500 nmol min-1

Synthesis of N-acetylglucosamine thiazoline/lipid II hybrids

Potential inhibitors of transglycosylases involved in bacterial cell wall biosynthesis were synthesized by combining N-acetylglucosamine thiazoline, a potent inhibitor of β-hexosaminidase, with functional groups present in lipid II, the natural substrate of the transglycosylases.