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The application of the 2-(chloroacetoxymethyl)benzoyl (CAMB) group to the O-protection of position 2 in glycosyl donors is described.Saponification of the phthalide and subsequent chloroacetylation of 2-(hydroxymethyl)benzoic acid (1) gave 2-(chloroacetoxymethyl)benzoic acid (2).Treatment of 2 with thionyl chloride afforded the acyl chloride 3.Acylation of O-2 of 1,3,4,6-tetra-O-acetyl-alpha-D-glucopyranose (4a), galactopyranose (4b) and of the amino group of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D-glucopyranose (4c) afforded the fully protected pyranose derivatives 5a-c in high yields.Compounds 5a and 5b were converted with HBr in acetic acid into the corresponding 2-O-CAMB-protected bromides 6a, b in excellent yields.Silver trifluoromethanesulfonate promoted glycosylation of the latter with 2-hydroxyethyl benzoate yielded the beta-glycosides 8a (74percent) and 8b (69percent).Direct activation of the glucosamine derivative 5c with ferric chloride gave the glucoside 8c (54percent).Furthemore, the galactosyl bromide 6b was coupled with methyl 2,3,4-tri-O-benzoyl-beta-D-glucopyranoside (11) affording the 2′-O-CAMB-protected methyl glycoside disaccharide 12 (63percent).Similarly, condensation of the glucosyl bromide 6a with 4a gave the beta-(1–>2)-linked disaccharide 13 (45percent).Treatment of compounds 8a and 13 with thiourea resulted in the deblocked glycosides 9a and 14.Similar deprotection of 8b gave 2-benzoyloxyethyl 3,4,6-tri-O-acetyl-beta-D-galactopyranoside (9b) and the 2-O-<2(hydroxymethyl)benzoyl> derivative 10.Reaction of 8c with thiourea afforded solely the dechloroacetylated glucoside 9c. – Key Words: Glycosylation / Protecting groups / Benzoyl, 2-chloroacetoxymethyl-

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The invention provides compounds with enhanced permeability for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc

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The invention is directed to compounds for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds, and methods of treating diseases and disorders related to deficiency or over expression of O-GlcNAcase, and/or accumulation or deficiency of O-GlcNAc

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Efficient and highly selective glycosylation reactions of peracetylated beta-D-N-acetylglucosamine are described using catalytic iron(III) triflate and 2,4,6-tri-tert-butylpyrimidine (TTBP) under microwave conditions. We have demonstrated that the formation of beta-(1?6) and beta-(1?3) linked disaccharides are obtained in high yields in the presence ofvarious protecting groups.

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Efficient and highly selective glycosylation reactions of peracetylated beta-D-N-acetylglucosamine are described using catalytic iron(III) triflate and 2,4,6-tri-tert-butylpyrimidine (TTBP) under microwave conditions. We have demonstrated that the formation of beta-(1?6) and beta-(1?3) linked disaccharides are obtained in high yields in the presence ofvarious protecting groups.

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The present disclosure concerns Bcl-xL inhibitors having low cell permeability, antibody drug conjugates (ADCs) comprising the inhibitors, synthons useful for synthesizing the ADCs, compositions comprising the inhibitors or ADCs, and various methods of using the inhibitors and ADCs.

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Having gained chemical understanding at molecular level, chemistry graduates may choose to apply this knowledge in almost unlimited ways, as it can be used to analyze all matter and therefore our entire environment. Like 10034-20-5, Name is (2S,3R,4R,5S,6R)-6-(Acetoxymethyl)-3-aminotetrahydro-2H-pyran-2,4,5-triyl triacetate hydrochloride. In a document type is Article, introducing its new discovery. Recommanded Product: 10034-20-5

The [N’-(2-chloroethyl)-N’-nitrosoamino]carbonyl [(2- chloroethyl)nitrosocarbamoyl, CNC] moiety containing compounds CNC- glycinamide 2d, CNC-amino acid derivatives 7a-d, and carbohydrate-CNC-amino acid conjugates 13, 18, 22, 23, 27, and 28 were synthesized and evaluated in vivo for their anticancer activities against the murine lymphocytic leukemia P388 using the National Cancer Institute (NCI) protocol. The most active compound was 2d with a 520% increase in life span (%ILS) and 6/6 survivors after 60 days. The CNC-amino acid analogs 7a-d possessed high to moderate activities with maximum %ILS values of 270, 174, 141 and 132, respectively. Among the carbohydrate-CNC-amino acid derivatives the alpha-methyl glycoside derivatives 22 and 23 were most active with maximum %ILS values of 277 and 137, respectively, followed by the hemiacetal carbohydrate analogs 13 and 18 with %ILS values of 93 and 149, respectively, and the tetra-O-acetyl derivatives 27 and 28 with %ILS of 110 and 111, respectively. Compounds 7b, 18, 23 and 28 were then tested in vivo against the murine lymphoid leukemia L1210 using the NCI protocol. In this case, the hemiacetal type carbohydrate- CNC-amino analog 18 had the highest activity with a maximum %ILS value of 477 and 4/6 survivors on day 60, followed by 7b (275% ILS), 23 (152% ILS) and 28 (106% ILS). The lipophilicities of all CNC compounds were determined by the partition coefficient using the UV method. A correlation of %ILS values with log P values indicated, in general, an increase in cytotoxicity with a decrease in hydrophilicity for the carbohydrate-CNC-amino acid conjugates 13, 18, 22, 23 and the clinical drugs streptozotocin (1e), chlorozotocin (1f), and cymerin (1g).

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Unprecedented regioselective glycosidations of 17beta-estradiol and nitro substituted derivatives thereof either at the phenol or carbinol position is reported. In the former case, glycosyl bromides or iodides were employed as the donors in a base promoted reaction conducted under two-phase conditions. In the latter case, glycosyl trichloroacetimidate donors were used in combination with the mild activation of 4 A acid washed molecular sieves. Georg Thieme Verlag Stuttgart.

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The O-GlcNAc modification involves the attachment of single beta-O-linked N-acetylglucosamine residues to serine and threonine residues of nucleocytoplasmic proteins. Interestingly, previous biochemical and structural studies have shown that O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from proteins, has an active site pocket that tolerates various N-acyl groups in addition to the N-acetyl group of GlcNAc. The remarkable sequence and structural conservation of residues comprising this pocket suggest functional importance. We hypothesized this pocket enables processing of metabolic variants of O-GlcNAc that could be formed due to inaccuracy within the metabolic machinery of the hexosamine biosynthetic pathway. In the accompanying paper (Bergfeld, A. K., Pearce, O. M., Diaz, S. L., Pham, T., and Varki, A. (2012) J. Biol. Chem. 287, 28865-28881), N-glycolylglucosamine (GlcNGc) was shown to be a catabolite of NeuNGc. Here, we show that the hexosamine salvage pathway can convert GlcNGc to UDP-GlcNGc, which is then used to modify proteins with O-GlcNGc. The kinetics of incorporation and removal of O-GlcNGc in cells occur in a dynamic manner on a time frame similar to that of O-GlcNAc. Enzymatic activity of O-GlcNAcase (OGA) toward a GlcNGc glycoside reveals OGA can process glycolyl-containing substrates fairly efficiently. A bacterial homolog (BtGH84) of OGA, from a human gut symbiont, also processes O-GlcNGc substrates, and the structure of this enzyme bound to a GlcNGc-derived species reveals the molecular basis for tolerance and binding of GlcNGc. Together, these results demonstrate that analogs of GlcNAc, such as GlcNGc, are metabolically viable species and that the conserved active site pocket of OGA likely evolved to enable processing of mis-incorporated analogs of O-GlcNAc and thereby prevent their accumulation. Such plasticity in carbohydrate processing enzymes may be a general feature arising from inaccuracy in hexosamine metabolic pathways.

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The N-glycosyl-iminocarboxylate complexes Cp*M(Cl)N(R)=C(R’)CO2 (M = Rh, Ir; R = glycosyl, R’ = Me, Ph, CH2CHMe2) with a chiral metal atom are formed in a template reaction from [Cp*MCl2]2 (M = Rh, Ir), the 2-keto carboxylic acid and tetra-O-acetyl-beta-D-glucosamine, D-glucosamine or D-glucamine as mixtures of two diastereoisomers and were characterized by analytical and spectroscopic methods.

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