[Glycosides of hydroxylamine derivatives. I. phase transfer synthesis and study of isatine-3-oximes glucosaminides influence on bacterial luminescence].

In the phase transfer system solid calcium carbonate-acetonitrile, per acetate alpha-D-glucosaminilchloride glycosilate easily deprotoned isatine-3-oximes hydroxyl groups. It was found that the presence in the reaction mixture a catalytic amounts of 15-crown-5 accelerated the process twice. Obtained O-beta-D-glucosaminides were identified with 1H-NMR spectroscopy. Features of synthesized compound's NMR spectra are discussed in comparison with those of another N-acetylglucosamine 1-O-derivatives. The biological activity of the some oximes with different substituents in isatin residuum has been studied in a test of inhibition of bioluminescence of marine luminescent bacteria Photobacterium leiognathi Sh12. The nature of N-substituent of isatin fragment and 5-substituent of isatin main structure is compared with glycosides ability to suppress bacterial luminescence.

[Synthesis of heteroaromatic N-beta-glycosides of N-acetylghicosamine under phase transfer conditions. III. 1,2,4-triazoIin-3-ones glucosaminides].

The catalytic phase transfer reactions of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-a-D-glucopyranosyl chloride with thiosubstituted 4-phenyl-5-R-thio-Delta2-1,2,4-triazolin-3-ones in solid alkali-organic solvent and in aqueous alkali-organic solvent were studied. The main products ofglucosaminilation reaction are the appropriate N-beta-glucosaminides. The effect of reaction conditions on the yield and composition of products formed was elucidated on the example of the reaction alpha-D-glucosaminyl chloride with 5-methylthio-4-phenyl-Delta2-1,2,4-triazolin-3-one. The optimal conditions of phase transfer glycosylation were established. N-1,2-trans-grycosidic bond formation was proved by 1H NMR and IR data as well as a comparison with spectral data obtained previously for the glycosides of similar structure.

[Neuro- and psychotropic activity of N-uronoylamino acids and N-uronoylpeptides].

Peculiarities of rat behavior were studied on a series of experimental stress models after systemic administration of new N-uronoyl derivatives of amino acids. The psychotropic effect was shown to be determined by the nature of the amino acid fragment. N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)-glycylglycine exhibited a more pronounced anxiolytic effect than pyracetam, whereas N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)-glycylglutamic acid is a stronger antidepressant than amitriptyline. Mechanisms of the psychotropic effects of the examined derivatives are discussed.

[Synthesis of heteroaromatic N-beta-glycosides of N-acetylglucosamine under phase transfer conditions: II].

Regioselective N-beta-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 (1)H NMR spectroscopy and X-ray analysis. The presence of a substituent at C7 of the aromatic ring leads to the formation of either a mixture of isomeric N-beta- and O-beta-D-glucosaminides or only oxazoline and/or 2-acetamidoglycal irrespective of the reaction conditions.

[Synthesis and biological activity of aryl S-beta-glycosides of 1-thio-N-acetylmuramyl-L-alanyl-D-isoglutamine].

Phenyl, p-tolyl, and p-tert-butylphenyl beta-1-thio-N-acetylglucosaminides were synthesized by the treatment of thiophenols with peracetate of alpha-D-glucosaminyl chloride in the presence of triethylamine or under the conditions of phase-transfer catalysis with quaternary ammonium salts. The compounds synthesized were used for obtaining of glycosides of 4,6-O-isopropylidene-N-acetylmuramic acid, which were coupled with L-Ala-D-Glu(NH2)-OBzl and then deprotected to obtain the target aryl beta-thioglycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). The aryl beta-thioglycosides of MDP were found to stimulate an antibacterial resistance toward Staphylococcus aureus in mice. The reliable induction of the spontaneous activity of natural killers in the population of blood mononuclear cells was observed only for phenyl beta-thio-MDP at a dose of 200 microg/ml. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

[Dialkylmethyl beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: synthesis and infection protective and cytotoxic activities].

Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic beta-glycosides of 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 beta-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 [beta]-MDPs at doses 2 microg/mice most effectively stimulated antibacterial resistance in mice against Staphylococcus aureus. In contrast to the previously synthesized undecan-6-yl beta-MDP, pentadecan-8-yl, nonadecan-10-yl, and tricosan-12-yl beta-MDPs demonstrated direct cytotoxicity toward tumor cells E-562 and blood mononuclear cells.

[Interferon-stimulating activity of muramoyl dipeptide glycosides].

The uninvestigated interferon (IFN)-inducing capacity of glycoside derivatives of N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been studied. Most MDP glycosides tested in vitro were more active than the reference preparation MDP. Under the in vivo conditions three studied preparations: MDP, a-heptyl-MDP and beta-(2-methyl-3-phenylchromonyl-7)-MDP stimulated production of considerable amount of circulating IFN that evidences for the promising character of their further investigation as preparations immunostimulators.

[Synthesis of heteroaromatic N-beta-glycosides of N-acetylglucosamine under the conditions of phase transfer catalysis: I. Glucosaminides of 2-oxobenzazoles].

Glycosylation of methylbenzoxazolone-2 and benzothiazolone-2 with the full acetate of alpha-D-glucosaminyl chloride in the phase transfer systems investigated (solid-organic solvent and aqueous alkali-organic solvent) regioselectively leads to the corresponding N-beta-D-glucosaminides, which is proved by 1H NMR spectroscopy and X-ray analysis.

[Glycosylation of 5-Phenyl-1,3,4-oxadiazole-2-thiol with alpha-D-glucopyranosyl chloride under phase transfer conditions].

5-Phenyl-1,3,4-oxadiazole-2-thiol is glycosylated easily and in high yields with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosyl chloride in the presence of catalytic amounts of aliphatic and aromatic crown ethers under phase transfer (solid-organic solvent) conditions. The reaction rate and the ratio of the resulting N- and S-regioisomers depend on the catalyst nature.

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

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

[Synthesis and protective activity of beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine with alkylalicyclic and arylaliphatic aglycons].

The following glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) were synthesized: beta-4-tert-butylcyclohexyl MDP, beta-2-(adamant-1-yl)ethyl MDP, beta-2,2-diphenylethyl MDP, and 3-2-(p-biphenyl)ethyl MDP. The starting peracetylated beta-N-acetylglucosaminides were prepared by the oxazoline method. They were converted into 4,6-O-isopropylidene-N-acetyl-D-muramic acids, which were coupled with L-Ala-D-Glu(NH2)OBn. The target glycopeptides were obtained after their deprotection. The stimulation of the antiinfection resistance of mice against Staphylococcus aureus by the MDP glycosides was studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.

[A synthesis of heteroaromatic S- and N-beta-glycosides of N-acetylglucosamine under phase transfer conditions].

The use of crown ethers for a phase transfer-catalyzed synthesis of heteroaromatic glycosides of N-acetylglucosamine was studied. The solid-liquid system and the catalysis by 15-crown-5 were found to provide for both a 100% conversion of the alpha-D-glucosaminyl chloride peracetate and a high reaction rate. The interaction of alpha-D-glucosaminyl chloride peracetate and oxadiazole and triazole mercapto derivatives capable of thiol-thione tautomerism carried out at room temperature in acetonitrile in the presence of anhydrous potassium carbonate and crown ethers was shown to lead to both S- and N-glycosides. The structures of the compounds synthesized were confirmed by X-ray analysis and 13C and 1H NMR spectroscopy.

[A phase-transfer glucosamination of phenols catalyzed by polyethylene glycol].

Glycosylation of phenols with alpha-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. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.

[Aromatic crown ethers as phase transfer catalysts in the synthesis of N-acetylglucosamine beta-aryl glycosides]. / Aromaticheskie kraun-éfiry kak katalizatory sinteza beta-arilglicozidov N-atsetilgliukozamina v mezhfaznykh usloviiakh.

The crown ether-catalyzed glycosylation of phenol, 4-methoxyphenol, and 4-nitrophenol was studied under phase transfer conditions in solid-liquid system. The asymmetric dibenzocrown esters are superior to [3.3]dibenzo-1 8-crown-6 and 15-crown-5 in the catalysis of these reactions. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

[N-acetylmuramyl-L-alanyl-D-isoglutamine glycosides. Effect of glycoside center configuration and aglycone nature on biological activity]. / Glikozidy N-atsetilmuramoil-L-alanil-D-izoglutamina. Vliianie konfiguratsii glikozidnogo tsentra i prirody aglikona na biologicheskuiu aktivnost'.

Hexyl, octyl, and cyclohexyl beta-glycosides and heptyl and cyclohexyl alpha-glycosides of muramyl dipeptide (MDP) were synthesized. Tests in vitro and in vivo revealed lower immunostimulating activities of MDP alpha-glycosides in comparison with the corresponding beta-glycosides and MDP itself. In the case of alkyl beta-glycosides, differences in hydrocarbon chain lengths (C4-C8) and in aglycone (aliphatic chain and aliphatic or aromatic ring) exerted no substantial effect on the immunostimulating activity.

[Effect of synthetic muramyl dipeptide derivatives on staphylococcal infection in mice]. / Vliianie sinteticheskikh proizvodnykh muramildipeptida na techenie stafilokokkovoi infektsii u myshei.

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-acetylglucosamine beta-aryl glycosides catalyzed by crown ethers]. / Kataliziruemyi kraun-soedineniiami sintez beta-arilglikozidov N-atsetilgliukozamina.

Glycosylation of phenols of various structure with alpha-D-glucosaminyl chloride peracetate in a solid phase-liquid system catalyzed by crown compounds was studied. The highest yields of aryl beta-glycosides were observed at room temperature in acetonitrile using anhydrous potassium carbonate as a base. The optimum phenol-glycosyl donor-base-crown ether ratio was 1:1:1:0.2.

[Synthesis of N-acetylmuramoyl-L-alanyl-D-isoglutamine beta-aryl glycosides]. / Sintez beta-arilglikozidov N-atsetilmuramoil-L-alanil-D-izoglutamina.

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.

[Synthesis and biological activity of anomeric muramoyldipeptide butylglycosides]. / Sintez i biologicheskaia aktivnost anomernykh butilglikozidov muramoildipeptida.

The synthesis of anomeric butyl glycosides of muramyl dipeptide was reported. alpha-Butyl glycoside of N-acetyl-D-glucosamine was 4,6-O-benzylidenated and the benzylidene derivative was 3-O-alkylated by the Williamson reaction with sodium (S)-2-chloropropionate. The resulting protected alpha-butyl glycoside of muramic acid was then condensed with L-Ala-D-iGln-OBzl by the DCC-HOSu method. Mild acidic hydrolysis and subsequent catalytic hydrogenolysis of the resulting glycopeptide yielded the target alpha-butyl glycoside of N-acetyl-L-alanyl-D-isoglutamine. In the synthesis of beta-butyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine, 2-acetamido- 4,6-di-O-acetyl-2-deoxy-3-O-[(R)-1-(methoxycarbonyl)ethyl]-alpha- D-glucopyranose, a 1-OH derivative of muramic acid, was the key compound. Its interaction with the excess thionyl chloride resulted in the corresponding glycosyl halide, which was condensed with n-butanol according to Helferich. O-Deacetylation, 4,6-isopropylidenation, and subsequent alkaline hydrolysis of the resulting compound gave the protected beta-butyl glycoside of muramic acid. Its activation and condensation with L-Ala-D-iGln-OBzl and the subsequent removal of protective groups were performed in the same manner as the reactions in the synthesis of alpha-butyl glycoside of N-acetyl-L-alanyl-D-isoglutamine. The adjuvant activity of the butyl glycosides to HIV proteins rgp160 and rgp120 and their ability to affect in vitro HIV replication and the proliferation of mouse spleen T-cells were examined. The biological activity of anomeric muramyl dipeptides was shown to depend essentially on the configuration of their anomeric center.

[Effect of saponins from Hedera taurica Carr. and modified muramylpeptides on replication of human immunodeficiency virus in vitro]. / Vliianie saponinov iz Hedera taurica Carr. i modifitsirovannykh muramilpeptidov na reproduktsiiu virusa immunodefitsita cheloveka in vitro.

The effects of muramyldipeptide (MDP), several new MDP derivatives, and saponins derived from Hedera taurica Carr, on the in vitro replication of HIV-1 were studied. The coefficient of alteration of the rate of HIV replication was used to compare these reagents' effects on virus replication in Jurkat-tat cells. This coefficient was calculated as the ratio of concentrations of HIV p24 in supernatants to the amount of viable cells. Muramylpeptides boosted HIV replication. Only one modified muramylpeptide alpha-butyl-MDP and tauroside H2 were not capable of boosting HIV-1 antigen production.