Skip to main content

Dialkylmethyl β-glycosides of N-acetylmuramyl-L-alanyl-D-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.

This is a preview of subscription content, access via your institution.



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


blood mononuclear cells


natural killers


  1. Baschang, G., Tetrahedron, 1989, vol. 45, pp. 6331–6360.

    CAS  Article  Google Scholar 

  2. Kusumoto, S., Inage, M., Shiba, T., Azuma, I., and Yamamura, Y., Tetrahedron Lett., 1978, no. 49, pp. 4899–4902.

  3. Kur’yanov, V.O., Zemlyakov, A.E., and Chirva, V.Ya., Bioorg. Khim., 1994, vol. 20, pp. 439–447.

    Google Scholar 

  4. Krivorutchenko, Yu.L., Andronovskaja, I.B., Hinkula, J., Krivoshein, Yu.S., Ljungdahl-Stahle, E., Pertel, S.S., Grishkovets, V.I., Zemlyakov, A.E., and Wahren, B., Vaccine, 1997, vol. 15, pp. 1479–1486.

    CAS  Article  PubMed  Google Scholar 

  5. Zemlyakov, A.E., Tsikalova, V.N., Tsikalov, V.V., Chirva, V.Ya., Mulik, E.L., and Kaluuzhin, O.V., Bioorg. Khim., 2006, vol. 32, pp. 424–431; Rus. J. Bioorg. Chem., 2006, vol. 32, pp. 382–388.

    Google Scholar 

  6. Lemieux, R.U. and Driguez, H., J. Am. Chem. Soc., 1975, vol. 52, pp. 4063–4068.

    Article  Google Scholar 

  7. Flowers, H.M. and Jeanloz, R.W., J. Org. Chem., 1963, vol. 28, pp. 2983–2986.

    CAS  Article  Google Scholar 

  8. Fermand-Jian, S., Perly, B., Level, M., and Lefrancier, P., Carbohydr. Res., 1987, vol. 162, pp. 23–32.

    CAS  Article  Google Scholar 

  9. Kalyuzhin, O.V., Mulik, E.L., Sergeev, V.V., Kalina, N.G., Elkina, S.I., Kalyuzhina, M.I., Kuzovlev, F.N., and Karaulov, A.V., Immunopatologiya, Allergologiya, Infektologiya, 2000, no. 4, pp. 73–77.

  10. Khaitov, R.M., Gushchin, I.S., Pinegin, B.F., and Zebrev, A.I., Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv (Handbook on the Experimental (Preclinical) Study of New Pharmacological Substances), Moscow: IIA Remedium, 2000, pp. 257–263.

    Google Scholar 

  11. Kusumoto, S., Okada, S., Yamamoto, K., and Shiba, T., Bull. Chem. Soc. Japan, 1978, vol. 51, pp. 2122–2126.

    CAS  Article  Google Scholar 

  12. Zemlyakov, A.E., Tsikalov, V.V., Kalyuzhin, O.V., Kur’yanov, V.O., and Chirva, V.Ya., Bioorg. Khim., 2003, vol. 29, pp. 316–322; Rus. J. Bioorg. Chem., 2003, vol. 29, pp. 286–292.

    Google Scholar 

  13. Davis, R. and Schultz, H.P., J. Org. Chem., 1962, vol. 27, pp. 854–857.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to A. E. Zemlyakov.

Additional information

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.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key words

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