- Convergent synthesis of novel muramyl dipeptide analogues: Inhibition of porphyromonas gingivalis-induced pro-inflammatory effects by high doses of muramyl dipeptide
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Porphyromonas gingivalis (P.g.)-induced TNF-α can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 μg/mL of MDP (MDP-low) up-regulated TNF-α by 29%, while 100
- Cai, Bin,Panek, James S.,Amar, Salomon
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p. 6878 - 6890
(2016/08/05)
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- Synthesis of 12 Stereochemically and Structurally Diverse C-Trisaccharides
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Cell surface carbohydrates and their analogs may be used to study the cellular interactions responsible for adhesion to pathogenic bacteria, viruses, and other cells and may represent leads for drug discovery. We have generated 12 C-trisaccharides (7-18) as potential inhibitors for the cell surface proteins of the bacterium Helicobactor pylori. The strategy used has resulted in the generation of C-trisaccharides structures that are represented by the formula Fuc-α(1-2)-hexose-(1-3)-GlcNAc where each of the 12 compounds possesses a central sugar that has been systematically replaced with stereochemically diverse structures, including D and L sugars, through de novo synthesis. This aroach relies upon an organometallic coupling of terminal monosaccharides 19 and 20 to prepare a "disaccharide" in a convergent manner. This intermediate is then divergently derivatized to form a variety of structural analogs about the central hexose. For the separable compounds, the assignment of stereochemistry was done using standard NMR techniques. In cases where inseparable diastereomeric mixtures were generated, we have described a novel recursive stereochemical deconvolution strategy. This recursive strategy is demonstrated in the diastereoselective synthesis of trisaccharides 14, subsequent to its initial rapid synthesis as a component of a diastereomeric mixture. Biological assays of these compounds should provide an insight into the binding requirements of carbohydrate receptors.
- Sutherlin, Daniel P.,Armstrong, Robert W.
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p. 5267 - 5283
(2007/10/03)
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- Synthesis of Compounds Designed To Inhibit Bacterial Cell Wall Transglycosylation
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Methods for preparation of compounds designed to inhibit the transglycosylation step in bacterial cell wall biosynthesis are described.Two hybrid structures (5 and 31) are synthesized, which combine features of the transglycosylase substrate with those of the natural product moenomycin, a known transglycosylation inhibitor.The compounds are synthesized by a convergent route involving the coupling as a phosphate diester of a protected sugar portion with a glycerate-lipid synthon.Details of the syntheses of the sugar and glycerate precursors are discussed.
- Hecker, Scott J.,Minich, Martha L.,Lackey, Karen
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p. 4904 - 4911
(2007/10/02)
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- AN ALTERNATIVE SYNTHESIS OF O-(2-ACETAMIDO-2-DEOXY-β-D-GLUCOPYRANOSYL)-(1-4)-N-ACETYLNORMURAMOYL-L-α-AMINOBUTANOYL-D-ISOGLUTAMINE
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Silver triflate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide (VIII) with benzyl 2-acetamido-6-O-benzoyl-2-deoxy-3-O-(methoxycarbonyl)-methyl-α-D-glucopyranoside (IV) afforded benzyl 2-acetamido-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-6-O-benzoyl-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside (IX) which, after deprotection, was converted into the acid XI.Condensation of acid XI with L-α-aminobutanoyl-D-isoglutamine benzyl ester and subsequent hydrogenolysis of the product XIII furnished compound XIV.Benzyl 2-acetamido-6-O-benzoyl-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside (IV) was prepared by partial benzoylation of benzyl 2-acetamido-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside (III) with benzoyl cyanide.
- Ledvina, Miroslav,Farkas, Jiri,Zajicek, Jaroslav,Jezek, Jan,Zaoral, Milan
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p. 2784 - 2794
(2007/10/02)
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- Synthesis of β(1-4)-Linked Disaccharides of N-Acetylglucosamine and3 N-Acetylmuramic Acid by Their Direct Condensation
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As a basic study in the synthetic approach to immunoactive cell wall peptid3oglycan whose backbone is a β(1-4)-linked saccharide of alternating glucosamine and3 muramic acid, methods for the direct condensation of these sugar components were studied and O-(N-acetyl-β-muramyl)-(1->4)-N-acetyl-D-glucosamine and O-(N-acetyl-β-D-glucosaminyl)-(1->4)-N-acetylmuramic acid were synthesized.In the synthesis of the latter disaccharide, previous formation of an ester bond between the carboxyl group of muramic acid and the 6-hydroxyl group of glucosamine proved to facilitate the glycoside bond formation between these sugar moieties.
- Kusumoto, Shoichi,Imoto, Masahiro,Oguki, Tsuyoshi,Shiba, Tetsuo
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p. 1419 - 1424
(2007/10/02)
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