Immunostimulating properties of synthetic derivatives of muramyl dipeptide and glucosaminyl muramyl dipeptide in vitro

Production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages of the spleen and peritoneal exudate of mice as well as cytotoxic factors (CFs) by murine splenocytes after in vitro activation was estimated. All the derivatives of muramyldipeptide (MDP) and glucosaminylmuramyldipeptide (GMDP) were able to induce production of TNF and CFs. In the presence of lipopolysaccharide (LPS), the effect was always higher. The response of the spleen macrophages to the effect of the preparations was higher than that of the peritoneal ones and ++non-fractionated splenocytes. GMDP and GMDP4 especially in the presence of LPS had the highest effect on induction of IL-1 by the murine peritoneal macrophages. On the contrary, MDP induced higher IL-1 synthesis by the spleen macrophages. The most active substances with respect to production of TNF, CFs and IL-1, i.e. MDP3 and GMDP4, might be recommended for immunotherapy of syngeneic tumors in animals.     

Aromatic crown ethers as phase transfer catalysts in the synthesis of N-acetylglucosamine beta-aryl glycosides

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.     

Synthesis of N-Acetylglucosamine Aryl β-Glycosides Catalyzed by Crown Compounds

Glycosylation of various phenols with -D-glucosaminyl chloride peracetate in a solid phase–liquid system catalyzed by crown compounds was studied. The highest yields of aryl -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.     

N-Acetylmuramyl-L-Alanyl-D-Isoglutamine Glycosides: Effect of Glycoside Bond Configuration and Aglycone on Biological Activity

Hexyl, octyl, and cyclohexyl -glycosides and heptyl and cyclohexyl -glycosides of muramyl dipeptide (MDP) were synthesized. Tests in vitro and in vivo revealed lower immunostimulating activities of MDP -glycosides in comparison with the corresponding -glycosides and MDP itself. In the case of alkyl -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.     

Glycosides of hydroxylamine derivatives: I. Phase transfer synthesis and the study of the influence of glucosaminides of isatine 3-oximes on bacterial luminescence

Easily deprotoned hydroxyl groups of isatine 3-oximes were glycosylated in high yields by α-D-glucosaminyl chloride peracetate in the solid potassium carbonate-acetonitrile phase transfer system. It was found that catalytic amounts of 15-crown-5 supported a twofold acceleration of the process. The resulting β-D-glucosaminides were identified by ¹H NMR spectroscopy. Specific features of the NMR spectra of the synthesized compounds are discussed in comparison with those of other l-O-derivatives of N-acetylglucosamine. Biological activities of oximes with different substituents in the isatin residue were studied by the bacterial luminescence inhibition test with marine luminescent bacteria Photobacterium leiognathi Sh1. The relationship of the structures of the isatin N-substituent and the 5-indolyl substituent and the glycoside capacity to suppress bacterial luminescence was analyzed.     

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.     

Aromatic Crown Ethers as Phase Transfer Catalysts in the Synthesis of N-Acetylglucosamine β-Aryl Glycosides

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-18-crown-6 and 15-crown-5 in the catalysis of these reactions.     

Synthesis of N-acetylglucosamine beta-aryl glycosides catalyzed by crown ethers]

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 and biological activity of aryl S-β-glycosides of 1-thio-N-acetylmuramyl-L-alanyl-D-isoglutamine

Phenyl, p-tolyl, and p-tert-butylphenyl β-1-thio-N-acetylglucosaminides were synthesized by the treatment of thiophenols with peracetate of α-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 β-thioglycosides of N-acetylmuramyl-L-analyl-D-isoglutamine (MDP). The aryl β-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 β-thio-MDP at a dose of 200 μg/ml. Original Russian Text ? A.E. Zemlyakov, V.N. Tsikalova, L.R. Azizova, V.Ya. Chirva, E.L. Mulik, M.V. Shkalev, O.V. Kalyuzhin, M.V. Kiselevsky, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 2, pp. 245–251.