Molecular Diversity

, Volume 15, Issue 4, pp 889–900 | Cite as

Synthesis of novel 6-triazologlycolipids via click chemistry and their preliminary cytotoxicity assessments

Full-Length Paper


Series of novel 6-triazole-linked galacto- or glucolipids were efficiently synthesized from O-benzylated sugar azides and various lipid alkynes via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click chemistry) followed by hydrogenolysis with PdCl2/H2. Subsequent MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay toward a panel of human cancer cell lines revealed that these triazologlycolipids possess low-to-modest toxicity on A549 (lung), MCF-7 (breast), HeLa (cervix), and HepG2 (liver). Furthermore, both the carbon chain length at the lipid end and the epimeric identity of the glycosyl moiety were determined to impact their corresponding bioactivity.


Glycolipid Click reaction Triazole Cytotoxicity MTT assay 


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  1. 1.
    Tsuji M (2006) Glycolipids and phospholipids as natural CD1d-binding NKT cell ligands. Cell Mol Life Sci 63: 1889–1898. doi: 10.1007/s00018-006-6073-z PubMedCrossRefGoogle Scholar
  2. 2.
    Wu D, Fujio M, Wong CH (2008) Glycolipids as immunostimulating agents. Bioorg Med Chem 16: 1073–1083. doi: 10.1016/j.bmc.2007.10.026 PubMedCrossRefGoogle Scholar
  3. 3.
    Piazza M, Rossini C, Fiorentina SD, Pozzi C, Comelli F, Bettoni I, Fusi P, Costa B, Peri F (2009) Glycolipids and benzylammonium lipids as novel antisepsis agents: synthesis and biological characterization. J Med Chem 52: 1209–1213. doi: 10.1021/jm801333m PubMedCrossRefGoogle Scholar
  4. 4.
    Ii K, Ichikawa S, Al-Dabbagh B, Bouhss A, Matsuda A (2010) Function-oriented synthesis of simplified caprazamycins: discovery of oxazolidine-containing uridine derivatives as antibacterial agents against drug-resistant bacteria. J Med Chem 53: 3793–3813. doi: 10.1021/jm100243n PubMedCrossRefGoogle Scholar
  5. 5.
    Zhang Z, Zong C, Song G, Lv G, Chun Y, Wang P, Ding N, Li Y (2010) Total synthesis of caminoside B, a novel antimicrobial glycolipid isolated from the marine sponge Caminus sphaeroconia. Carbohydr Res 345: 750–760. doi: 10.1016/j.carres.2010.01.015 PubMedCrossRefGoogle Scholar
  6. 6.
    Vogel J, Bendas G, Bakowsky U, Hummel G, Schimidt RR, Ketmann U, Rothe U (1998) The role of glycolipids in mediating cell adhesion: a flow chamber study. Biochim Biophys Acta 1372: 205–215. doi: 10.1016/S0005-2736(98)00058-3 PubMedCrossRefGoogle Scholar
  7. 7.
    Falconer RA, Toth I (2007) Design, synthesis and biological evaluation of novel lipoamino acid-based glycolipids for oral drug delivery. Bioorg Med Chem 15: 7012–7020. doi: 10.1016/j.bmc.2007.07.048 PubMedCrossRefGoogle Scholar
  8. 8.
    de Almeida MV, Hyaric ML (2005) Carbohydrate-derived surfactants. Mini-Rev Org Chem 2: 283–297. doi: 10.2174/1570193054368873 CrossRefGoogle Scholar
  9. 9.
    Thiesen PH, Rosenfeld H, Konidala P, Garamus VM, He L, Prange A, Niemeyer B (2006) Glycolipids from a colloid chemical point of view. J Biotechnol 124: 284–301. doi: 10.1016/j.jbiotec.2006.03.032 PubMedCrossRefGoogle Scholar
  10. 10.
    Paul KJV, Loganathan D (2008) Synthesis of novel glycolipids derived from glycopyranosyl azides and N-(β-glycopyranosyl)azidoacetamides. Tetrahedron Lett 49: 6356–6359. doi: 10.1016/j.tetlet.2008.08.073 CrossRefGoogle Scholar
  11. 11.
    Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40: 2004–2021. doi: 10.1002/1521-3773(20010601) CrossRefGoogle Scholar
  12. 12.
    Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41: 2596–2599. doi: 10.1002/1521-3773(20020715) CrossRefGoogle Scholar
  13. 13.
    Neto V, Granet R, Krausz P (2010) Novel class of non-ionic monocatenary and bolaform alkylglycoside surfactants. Synthesis by microwave-assisted glycosylation and olefin cross-metathesis or by ‘click-chemistry’: physicochemical studies. Tetrahedron 66: 4633–4646. doi: 10.1016/j.tet.2010.03.115 CrossRefGoogle Scholar
  14. 14.
    Lee T, Cho M, Ko SY, Youn HJ, Baek DJ, Cho WJ, Kang CY, Kim S (2007) Synthesis and evaluation of 1,2,3-triazole containing analogues of the immunostimulant α-GalCer. J Med Chem 50: 585–589. doi: 10.1021/jm061243q PubMedCrossRefGoogle Scholar
  15. 15.
    Song SX, Zhang HL, Kim CG, Sheng Li, He XP, Long YT, Li J, Chen GR (2010) Expeditious preparation of triazole-linked glycolipids via microwave accelerated click chemistry and their electrochemical and biological assessments. Tetrahedron 66: 9974–9980. doi: 10.1016/j.tet.2010.10.033 CrossRefGoogle Scholar
  16. 16.
    Adams S, Kaufmann F (1991) A new class of potent antiproliferative glycolipids. Chem Phys Lipids 59: 255. doi: 10.1016/0009-3084(91)90025-7 CrossRefGoogle Scholar
  17. 17.
    Maeda N, Kokai Y, Ohtani S, Sahara H, Hada T, Ishimaru C, Kuriyama I, Yonezawa Y, Iijima H, Yoshida H, Sato N, Mizushina Y (2007) Anti-tumor effects of the glycolipids fraction from Spinach which inhibited DNA polymerase activity. Nutr Cancer 57: 216–223. doi: 10.1080/01635580701277908 PubMedCrossRefGoogle Scholar
  18. 18.
    Jung M, Lee Y, Moon HI, Jung Y, Jung H, Oh M (2009) Total synthesis and anticancer activity of highly potent novel glycolipid derivatives. Eur J Med Chem 44: 3120–3129. doi: 10.1016/j.ejmech.2009.03.007 PubMedCrossRefGoogle Scholar
  19. 19.
    Samadder P, Bittman R, Byun HS, Arthur G (2009) A glycosylated antitumor ether lipid kills cells via paraptosis-like cell death. Biochem Cell Biol 87: 401–414. doi: 10.1139/O08-147 PubMedCrossRefGoogle Scholar
  20. 20.
    Maeda N, Kokai Y, Ohtani S, Sahara H, Kumamoto-Yonezawa Y, Kuriyama I, Hada T, Sato N, Yoshida H, Mizushina Y (2008) Anti-tumor effect of orally administered spinach glycolipid fraction on implanted cancer cells, Colon-26, in mice. Lipids 43: 741–748. doi: 10.1007/s11745-008-3202-5 PubMedCrossRefGoogle Scholar
  21. 21.
    de la Sovera V, Bellomo A, Pena JM, Gonzalez D, Stefani HA (2011) Expanding cyclitol structural diversity by biocatalysis and metalocatalysis. A click chemistry approach. Mol Divers 15: 163–172. doi: 10.1007/s11030-010-9237-6 PubMedCrossRefGoogle Scholar
  22. 22.
    Pirali T, Faccio V, Mossetti R, Grolla AA, Micco SD, Bifulco G, Genazzani AA, Tron GC (2010) Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition. Mol Divers 14: 109–121. doi: 10.1007/s11030-009-9153-9 PubMedCrossRefGoogle Scholar
  23. 23.
    Lin L, Shen Q, Chen GR, Juan X (2008) Synthesis of triazole-linked β−C-glycosyl dimers as inhibitors of PTP1B. Bioorg Med Chem 16: 9757–9763. doi: 10.1016/j.bmc.2008.09.066 PubMedCrossRefGoogle Scholar
  24. 24.
    Zhang YJ, He XP, Li C, Li Z, Shi DT, Gao LX, Qiu BY, Shi XX, Tang Y, Li J, Chen GR (2010) Triazole-linked benzylated glucosyl, galactosyl, and mannosyl monomers and dimers as novel sugar scaffold-based PTP1B inhibitors. Chem Lett 39: 1261–1263. doi: 10.1246/cl.2010.1261 CrossRefGoogle Scholar
  25. 25.
    Cheng KG, Liu J, Liu X, Sun H, Xie J (2009) Synthesis of glucoconjugates of oleanolic acid as inhibitors of glycogen phosphorylase. Carbohydr Res 344: 841–850. doi: 10.1016/j.carres.2009.02.012 PubMedCrossRefGoogle Scholar
  26. 26.
    Kobertz WR, Bertozzi CR, Bednarski MD (1996) C-glycosyl aldehydes: synthons for C-linked disaccharides. J Org Chem 61: 1894–1897. doi: 10.1021/jo9517095 PubMedCrossRefGoogle Scholar
  27. 27.
    Li SC, Meng XB, Cai MS, Li ZJ (2006) Optimized procedure for the synthesis of 6-azido-6-deoxy-galactopyranosides from 6-O-tosyl-galactopyranosides. Synth Commun 36: 637–643. doi: 10.1080/00397910500408787 CrossRefGoogle Scholar
  28. 28.
    Masaki Y, Tanaka N, Miura T (1997) Mild esterification and transesterification of carboxylic acids catalyzed by tetracyanoethylene and dicyanoketene dimethyl acetal. Chem Lett 26: 55–56. doi: 10.1246/cl.1997.55 CrossRefGoogle Scholar
  29. 29.
    Qu F, Hong JH, Du J, Newton MG, Chu CK (1999) Asymmetric synthesis of (2’R, 4’R) and (2’S, 4’S)-1, 3-dioxolanyl triazole C-nucleosides. Tetrahedron 55: 9073–9088. doi: 10.1016/S0040-4020(99)00499-8 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Hai-Lin Zhang
    • 1
  • Xiao-Peng He
    • 1
    • 3
  • Li Sheng
    • 2
  • Yuan Yao
    • 1
  • Wei Zhang
    • 2
  • Xiao-Xin Shi
    • 1
  • Jia Li
    • 2
  • Guo-Rong Chen
    • 1
  1. 1.Key Laboratory for Advanced Materials and Institute of Fine Chemicals, and School of PharmacyEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  2. 2.National Center for Drug Screening, State Key Laboratory of Drug ResearchShanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Chinese Academy of SciencesShanghaiPeople’s Republic of China
  3. 3.PPSM, ENS CachanCNRSCACHANFrance

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