Synthesis and protective anti-infective action of anomeric lipophilic glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine

Anomeric pairs of α-and β-dodecyl, α-and β-(1-pentylhexyl), and α-and β-cyclododecyl glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) were synthesized. The starting β-D-glucosaminides were obtained by the oxazoline method, and the corresponding α-isomers, by the mercuric iodide-catalyzed glycosylation of alcohols with α-glucosaminyl chloride peracetate in nitromethane at ～90°C. No reliable differences between the stimulation of mouse resistance to the infection with Staphylococcus aureus (doses of 2, 20, and 200 μg/mouse) and Escherichia coli (doses of 0.05, 1, and 20 μg/mouse) with the MDP α-and β-glycosides were found.     

Dialkylmethyl β-glycosides of <Emphasis Type="Italic">N</Emphasis>-acetylmuramyl-<Emphasis Type="Italic">L</Emphasis>-alanyl-<Emphasis Type="Italic">D</Emphasis>-isoglutamine: Synthesis and protective antiinfection and cytotoxic activities

Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic glycosides of β-N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). Pentadecan-8-ol, nonadecan-10-ol, and tricosan-12-ol were glycosylated by the oxazoline method. Based on the corresponding glucosaminides, alkyl β-glycosides of 4,6-O-isopropylidene-N-acetylmuramic acid were synthesized and coupled with the dipeptide. Deprotection of isopropylidene groups by acidic hydrolysis and catalytic hydrogenolysis of benzyl esters resulted in the target muramyldipeptide glycosides. Nonadecan-10-yl and tricosan-12-yl β-MDPs at doses 2 μg/mice most effectively stimulated antibacterial resistance in mice against Staphylococcus aureus. In contrast to the previously synthesized undecan-6-yl β-MDP, pentadecan-8-yl, nonadecan-10-yl, and tricosan-12-yl β-MDPs demonstrated direct cytotoxicity toward tumor cells K-562 and blood mononuclear cells.     

Synthesis of heteroaromatic <Emphasis Type="Italic">N</Emphasis>-β-glycosides of <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine under phase transfer conditions: II. Indolin-2-one glycosaminides

Regioselective N-β-glucosamination of various unsubstituted or C4-, C5-, or C6-monosubstituted indolin-2-ones under phase transfer conditions was studied. The regioselectivity was unambiguously proved by ¹H NMR spectroscopy and X-ray analysis. The presence of substituent at C7 of the aromatic ring leads to the formation of either a mixture of isomeric N-β-and O-β-D-glucosaminides, or only oxazoline and/or 2-acetamidoglycal irrespective of the reaction conditions.     

Effect of synthetic muramyl dipeptide derivatives on staphylococcal infection in mice

The work deals with the results of experimental evaluation of the influence of some new modified derivatives of muramyldipeptide (MDP) on the course of staphylococcal infection in mice. The preparations under study were found to produce rapid elimination of bacteria from kidneys and the increase of phagocytic activity of blood macrophages in animals. At the same time MDP and its derivatives stimulated natural killer cells whose activity was inhibited during infection. The dependence between the structure of these compounds and their protective action in staphylococcal infection, as well as the increase of the natural immunity characteristics of the body was followed.     

Synthesis of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine Aryl β-Glycosides

Synthesis of N-acetylmuramyl-L-alanyl-D-isoglutamine phenyl and (2-naphthyl) -glycosides, novel muramyl dipeptide derivatives with phenolic aglycons, was reported. The starting N-acetylglucosamine aryl glycosides were obtained by glycosylation of phenols with peracetylated -glucosaminyl chloride under the conditions of phase-transfer catalysis and used for the synthesis of 4,6-O-isopropylidene-N-acetylmyramic acid aryl -glycosides. Condensation of these derivatives with a dipeptide and subsequent deprotection resulted in the intended glycopeptides.     

A Phase-Transfer Glucosamination of Phenols Catalyzed by Polyethylene Glycol

Glycosylation of phenols with α-D-glucosaminyl chloride peracetate catalyzed by polyethylene glycol (PEG) was carried out in a solid-liquid phase transfer system at room temperature. The results were compared with those previously obtained for the catalysis with various crown ethers. The catalytic activity of PEG in this reaction was found to be comparable with those of 15-crown-5 and aromatic crown ethers.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 3, 2005, pp. 335–336.Original Russian Text Copyright © 2005 by Kur’yanov, Priskoka, Chupakhina, Chirva.     

Synthesis of N-acetylmuramoyl-L-alanyl-D-isoglutamine beta-aryl glycosides]

Synthesis of N-acetylmuramyl-L-alanyl-D-isoglutamine phenyl and naphthyl-2 beta-glycosides, novel muramyl dipeptide derivatives with phenolic aglycones, was reported. The starting N-glucosamine aryl glycosides were obtained by glycosylation of phenols with peracetylated alpha-glucosaminyl chloride under the conditions of phase-transfer catalysis and used for the synthesis of 4,6-O-isopropylidene-N-acetylmyramic acid aryl beta-glycosides. Condensation of these derivatives with a dipeptide and subsequent deprotection resulted in the target glycopeptides.     

The synthesis of <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine heteroaromatic <Emphasis Type="Italic">N</Emphasis>-β-glycosides under phase transfer conditions: Part III. 1,2,4-triazolin-3-one glucosaminides

Reactions of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chloride with thiosubstituted 5-thio-4-phenyl-Δ²-l,2,4-triazolin-3-ones were studied in solid alkali-organic solvent and aqueous alkali-organic solvent catalytic phase transfer systems. The major products of glucosaminylation were the appropriate N-β-glucosaminides. The effects of reaction conditions on the product yield and composition were studied with the reaction α-D-glucosaminyl chloride with 5-methylthio-4-phenyl-Δ²-l,2,4-triazolin-3-one. Optimal conditions of interphase glycosylation were found. The formation of N-l,2-trans-glycosidic bond was proved by ¹H NMR and IR data as well as by comparison with the published spectral data for glycosides of similar structures.