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Dialkylmethyl β-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: Synthesis and protective antiinfection and cytotoxic activities

Abstract

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.

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Abbreviations

MDP:

N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide)

BMC:

blood mononuclear cells

NK:

natural killers

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Correspondence to A. E. Zemlyakov.

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Original Russian Text © A.E. Zemlyakov, V.N. Tsikalova, V.V. Tskalov, V.Ya. Chirva, E.L. Mulik, F.N. Kuzovlev, O.V. Kalyuzhin, M.V. Kiselevsky, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 1, pp. 114–120.

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Zemlyakov, A.E., Tsikalova, V.N., Tsikalov, V.V. et al. Dialkylmethyl β-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: Synthesis and protective antiinfection and cytotoxic activities. Russ J Bioorg Chem 34, 103–109 (2008). https://doi.org/10.1134/S1068162008010147

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  • DOI: https://doi.org/10.1134/S1068162008010147

Key words

  • antibacterial resistance
  • cytotoxicity
  • glycopeptides
  • muramyl dipeptide glycosides
  • oxazoline method