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

Russian Journal of Bioorganic Chemistry volume 34, pages 103–109 (2008)Cite this article

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

References

  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

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Authors and Affiliations

  1. Vernadsky Tauric National University, Vernadsky pr. 4, Simferopol, 95007, Ukraine

    A. E. Zemlyakov, V. N. Tsikalova, V. V. Tsikalov & V. Ya. Chirva

  2. Research Institute of Human Morphology, Russian Academy of Medical Sciences, ul. Tsurupy 3, Moscow, 117418, Russia

    F. N. Kuzovlev & O. V. Kalyuzhin

  3. Research Institute of Experimental Diagnostics and Cancer Therapy, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse 24, Moscow, 115478, Russia

    E. L. Mulik & M. V. Kiselevsky

Authors
  1. A. E. Zemlyakov
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  2. V. N. Tsikalova
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  3. V. V. Tsikalov
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  4. V. Ya. Chirva
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  5. E. L. Mulik
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  6. F. N. Kuzovlev
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  7. O. V. Kalyuzhin
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  8. M. V. Kiselevsky
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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.

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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