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Synthesis and biological evaluation of new UDP-GalNAc analogues for the study of polypeptide-alpha-GalNAc-transferases

A series of three O-methylated UDP-GalNAc analogues have been synthesised using a divergent strategy from a 3,6-di-O-pivaloyl GlcNAc derivative. The biological activity of these probes toward polypeptide-alpha-GalNAc-transferase T1 has been investigated. This study shows that this glycosyltransferase exhibits a very high substrate specificity.

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Tetrahydropyran – Wikipedia,
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USE OF N-ACETYL-D-AMINOGLYCOSAMINE IN TREATMENT OF NON-SPECIFIC INFLAMMATIONS RELATED TO PHYSICAL OR CHEMICAL FACTORS

The present invention relates to a use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating non-specific inflammations caused by physical/chemical factors and controlling symptoms thereof. A preparation comprising N-acetyl-D-glucosamine as main active component for treating non-specific inflammations caused by physical/chemical factors exhibits merits of significant therapeutical effects and simple manufacture and has no side effect.

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Tetrahydropyran – Wikipedia,
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De novo chemoenzymatic synthesis of sialic acid

A chemoenzymatic synthesis of sialic acid from inexpensive N-acetyl-D-glucosamine is described. In a three-step Wittig-protection- ozonolysis strategy manno-configured aldehydes are obtained. Treatment with oxaloacetate in the presence of macrophomate synthase affords the signature alpha-keto-gamma-hydroxy acid moiety with high diastereoselectivity. The Royal Society of Chemistry.

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Tetrahydropyran – Wikipedia,
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De novo design of a trans-beta-N-acetylglucosaminidase activity from a GH1 beta-glycosidase by mechanism engineering

Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable beta-glycosidase into an exo-beta-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural beta-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the beta-glycosidase from Thermus thermophilus (TtbetaGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtbetaGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(beta-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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2-Acetamido-1,2-dideoxynojirimycin: An improved synthesis

The potent beta-N-acetylglucosaminidase inhibitor, 2-acetamido-1,2-dideoxynojirimycin, was prepared in 6 steps from N-acetyl-D-glucosamine (overall yield 10%) via the double reductive amination of a keto aldehyde as the key step.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Central neural tumor destruction by controlled release of a synthetic glycoside dispersed in a biodegradable polymeric matrix

An octyl N-acetylglucosaminide derivative with a pentaerythritol chain at position 6 has been synthesized and evaluated as an inhibitor of neural tumor growth. The glycoside inhibited the growth of a neuroectodermic tumor implanted in rats and, when loaded on a slow-delivery polymer disk, caused the destruction of cultured human astroblastoma obtained after surgical biopsy.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Synthesis and Some Transformations of 2-Acetamido-5-amino-3,4,6-tri-O-benzyl-2,5-dideoxy-D-glucono-1,5-lactam

The lactam 21 was obtained in an overall yield of 72% from the hydroxy amide 16 by oxidation with the Dess-Martin periodinane, acid-catalysed isomerization of the oxidation products in toluene, whereupon 18/19 precipitated, and reductive dehydroxylation of 18/19 (Et3SiH/BF3 ¡¤ OEt2; Scheme 1). The amide 16 was obtained by ammonolysis of the N-acetylglucosamine-derived lactone 15. Depending on the oxidation method, 16 yielded the keto amide 17, the hydroxy lactams 18/19, and the pyrrolidinecarboxamide 20 in widely different proportions. The pyrrolidinecarboxamide 20 was not reduced under the conditions of the reductive dehydroxylation. Hydrogenolysis of the benzyl-protected lactam 21 gave the trihydroxy lactam 22, while reduction with NaBH4/ BF3 ¡¤ OEt2 led to the 2-acetamidopiperidine derivative 24 (Scheme 2). Selective (tert-butoxy)carbonylation of the lactam 21 (? 25) followed by NaBH4 reduction and acid-catalysed solvolysis in EtOH led to the alpha-ethoxycarbamates 28/29. Similarly, (tert-butoxy)carbonylation of 1 (? 31) followed by reduction to 32/33 and glycosidation yielded the ethoxycarbamate 34. Treatment of the GlcNAc-derived ethyl glycosides 28/29 with Me3SiCN/ BF3 ¡¤ OEt2 gave the equatorial amino nitrile 30. Under similar conditions, the Glc-derived glycoside 34 led to the iminooxazolidinone 35. In the presence of a larger proportion of Me3SiCN at 5, 34 was transformed into the axial, selectively monodebenzylated amino nitrile 36.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Effect of sub- and supercritical water pretreatment on enzymatic degradation of chitin

We examined the effect of sub- and supercritical water pretreatment (300-400 C, 0.5-15 min) on enzymatic degradation of chitin to N,N?-diacetylchitobiose (GlcNAc)2. The yield of (GlcNAc) 2 by enzymatic degradation of supercritical water pretreated chitin at 400 C for 1.0 min was up to 37%, compared to 5% without the pretreatment. X-ray diffraction (XRD) analysis revealed that the d-spacing and the crystallite size increased by sub- and supercritical water pretreatment, which is indicative of swelling of the chitin. The swelling of the chitin crystal structure improved enzymatic degradation by allowing the enzymes easy access to the chitin.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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2-Acetamido-2-deoxy-l-iminosugar C-Alkyl and C-Aryl Glycosides: Synthesis and Glycosidase Inhibition

The synthesis of a series of six-membered 2-acetamido l-iminosugar C-alkyl and C-aryl glycosides is reported. A diastereoselective sugar-ring enlargement/C-alkylation (or arylation) /ring-contraction sequence applied to d-gluco- and d-manno-configured 2-acetamido azidolactols provides new l-iminosugar C-glycosides. The 1,2-trans stereocontrolled introduction of the pseudoanomeric substituent in these heterocycles strongly suggests a NHAc neighbouring-group participation. In their deprotected form, the nine iminosugars exhibit moderate hexosaminidases and beta-glucuronidase inhibition.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Determination of N-acetylglucosamine in cosmetic formulations and skin test samples by hydrophilic interaction liquid chromatography and UV detection

N-Acetylglucosamine is an ingredient in pharmaceuticals, nutritional supplements and in cosmetics. N-Acetylglucosamine in cosmetics is expected to improve skin hydration, reparation, and to contribute as anti-wrinkle agent. This study reports on the validation and application of an HPLC method based on HILIC and UV detection for determining N-acetylglucosamine in cosmetics and in samples obtained after testing the skin exposed to cosmetics formulations. The chromatographic column used is a ZIC-pHILIC (150mm¡Á4.6mm, 5mum particle size) on which a mobile phase containing acetonitrile-aqueous KH2PO4 (70:30, v/v) 15mM was applied in isocratic elution mode injecting 20mul of sample at 0.5ml/min constant flow-rate and 10¡À1C column temperature. Under these conditions the total run time was 10min and N-acetylglucosamine eluted baseline separated from all other compounds in the samples. Calibration in the range from 40 to 80mug/ml allowed to assess the method linearity (R2>0.999) in a concentration range corresponding to about 50% to 120% of the expected levels of N-acetylglucosamine in the formulations. Precision expressed by RSD% was always better than 2% in intra-day and inter-day assays of authentic samples. Accuracy was in all cases within 95-105% of the expected concentration value in formulations containing N-acetylglucosamine. The sensitivity of the method was at the level of 10mug/ml as limit of detection, and at 40mug/ml as limit of quantitation. The application of the method to formulations containing solid lipid nanoparticles documents its usefulness in cosmetic quality control. The results witness that the method is also suitable for the determination of N-acetylglucosamine in samples obtained from skin test strips.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics