• Marco Brito-Arias


C-glycosides have attracted much attention, considering that many of them have demonstrated their effectiveness as therapeutic agents. The increasing significance of C-glycosides is that the conformational differences compared to O- or N-glycosides are minimal, and that they are resistant to enzymatic or acidic hydrolysis since the anomeric center has been transformed from acetal to ether [1]. A glycoside is defined as C-glycoside when what is supposed to be the anomeric carbon of a sugar is interconnected to the aglycon, generating a new C–C bond. According to Levy and Tang [2] the term C-glycoside describes those structures in which a common structural motifs the presence of carbon functionality at what would otherwise be the anomeric position of a sugar or derivative. Structurally C-glycosides can be constituted by aliphatic, or aromatic aglycon, and the sugar can be pyranose or furanose. A variety of natural product C-glycosides have been described. Examples of C-glycosides isolated from different plant genera or insects and characterized spectroscopically are: Carminic acid (cochineal), Aloin (Aloe vera), Scoparin (Cytisus scoparius), Saponarin (Saponaria officinalis), flavonoid phytoalexins such as Cucumerins (Cucumis sativus) and Naringenin (grapefruit), [3] C-glucosyl xanthones [4], and complex benzoquinone Altromycin B [5] (actinomycetes), among others (Scheme 5.1).


Anomeric Carbon Glycosyl Donor Carminic Acid Mitsunobu Reaction Sigmatropic Rearrangement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Belica PS, Franck RW (1998) Benzylic C-glycosides via the Ramberg-Backlund reaction. Tetrahedron Lett 39:8225–8228CrossRefGoogle Scholar
  2. 2.
    Levy DE, Tang C (1995) The chemistry of C-glycosides. Pergamon Press, OxfordGoogle Scholar
  3. 3.
    McNally DJ, Wurms KV, Labbé C, Quideau S, Belanger RR (2003) Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus. J Nat Prod 66:1280–1283CrossRefGoogle Scholar
  4. 4.
    Pauletti PM, Castro-Gamboa I, Siqueira-Silva DH, Marx-Young MC, Tomazela DM, Eberlin MN, da Silva-Bolzani V (2003) New antioxidant C-glucosylxanthones from the stems of Arrabidaea samydoides. J Nat Prod 66:1384–1387CrossRefGoogle Scholar
  5. 5.
    Pasetto P, Franck W (2003) Synthesis of both possible isomers of the northwest quadrant of altromycin B. J Org Chem 68:8042–8060CrossRefGoogle Scholar
  6. 6.
    Dolle RE, Niclolaou KC (1985) Total synthesis of elfamycins: aurodox and efrotomycin. 1. Strategy and construction of key intermediates. J Am Chem Soc 107:1691–1694CrossRefGoogle Scholar
  7. 7.
    Ireland RE, Anderson RC, Badoub R, Fitzsimmons B, McGarvey S, Thaissivongs S, Wicox CS (1983) The total synthesis of ionophore antibiotics. A convergent synthesis of lasalocid A (X537A). J Am Chem Soc 105:1988–2006CrossRefGoogle Scholar
  8. 8.
    Emery F, Vogel P (1993) Total synthesis of undeculofuranosiduronic acid derivatives related to herbicidins. Tetrahedron Lett 34:4209–4212CrossRefGoogle Scholar
  9. 9.
    Paterson L, Keown LE (1997) Studies in marine macrolide synthesis: stereocontrolled synthesis of the F-ring subunit of spongistatin 1 (altohyrtin A). Tetrahedron Lett 38:5727–5730CrossRefGoogle Scholar
  10. 10.
    Lewis MD, Cha JK, Kishi Y (1982) Highly stereoselective approaches to a- and b-C-glycopyranosides. J Am Chem Soc 104:4976–4978CrossRefGoogle Scholar
  11. 11.
    Du Y, Linhardt RJ, Vlahov I (1998) Recent advances in stereoselective C-gylcoside synthesis. Tetrahedron 54:9913–9959CrossRefGoogle Scholar
  12. 12.
    Postema MHD (1995) C-glycoside synthesis. CRC Press, Boca Raton, FLGoogle Scholar
  13. 13.
    Sinaÿ P (1997) Synthesis of oligosaccharide mimetics. Pure Appl Chem 69:459–463CrossRefGoogle Scholar
  14. 14.
    Postema MHD (1992) Recent developments in the synthesis of C-glycosides. Tetrahedron 48:8545–8599CrossRefGoogle Scholar
  15. 15.
    Gervay J, Hadd MJ (1997) Utilization of ELISA technology to measure biological activities of carbohydrates relevant in disease states. Current medicinal chemistry. J Org Chem 62:6961–6967CrossRefGoogle Scholar
  16. 16.
    Lin L, He X-P, Xu Q, Chen G-R, Xie J (2008) Synthesis of β-C-glycopyranosyl-1,4-naphthoquinone derivatives and their cytotoxic activity. Carbohydr Res 343:773–779CrossRefGoogle Scholar
  17. 17.
    Liu Z, Byun H-S, Bittman R (2010) Synthesis of immunostimulatory α-C-galactosylceramide glycolipids via sonogashira coupling, asymmetric epoxidation, and trichloroacetimidate-mediated epoxide opening. Org Lett 12:2974–2977CrossRefGoogle Scholar
  18. 18.
    Oyama K, Kondo TJ (2004) Total synthesis of flavocommelin, a component of the blue supramolecular pigment from Commelina communis, on the basis of direct 6-C-glycosylation of flavane. J Org Chem 69:5240–5246CrossRefGoogle Scholar
  19. 19.
    Calzada E, Clarke CA, Roussin-Bouchard C, Wightman RH (1995) Synthesis of C-glycofuranosides by the stereoselective reduction of hemiacetals. J Chem Soc Perkin 1 517–518Google Scholar
  20. 20.
    Oddo A, Holl R (2012) Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue. Carbohydr Res 359:59–64CrossRefGoogle Scholar
  21. 21.
    Srinivas B, Reddy TR, Kashyap S (2015) Ruthenium catalyzed synthesis of 2,3-unsaturated C-glycosides from glycals. Carbohydr Res 406:86–92CrossRefGoogle Scholar
  22. 22.
    McGarvey G, LeClair CA, Schmidtmann BA (2008) Studies on the stereoselective synthesis of C-allyl glycosides. Org Lett 10:4727–4730CrossRefGoogle Scholar
  23. 23.
    Schmidt RW, Frick B, Haag-Zeino B, Apparao S (1987) C-aryl-glycosides and 3-deoxy-2-glyculosonates via inverse type hetero-Diels-Alder reaction. Tetrahedron Lett 28:4045–4048CrossRefGoogle Scholar
  24. 24.
    Lancelin JM, Sinaÿ P (1985) Use of selenium in carbohydrate chemistry: preparation of C-glycoside congeners. Carbohydr Res 136:369–374CrossRefGoogle Scholar
  25. 25.
    Craig D, Pennington MW, Warner P (1999) Stereoselective synthesis of substituted tetrahydrofurans using 5-endo-trig cyclisation reactions. Tetrahedron 55:13495–13512CrossRefGoogle Scholar
  26. 26.
    Khan AT, Sharma P, Schmidt RR (1995) Synthesis of C-disaccharides: an unusual ring closure reaction. Carbohydr Res 14:1353–1367CrossRefGoogle Scholar
  27. 27.
    Tius MA, Gomez-Galano J, Gu X, Zaidi JH (1991) C-Glycosylanthraquinone synthesis: total synthesis of vineomycinone B2 methyl ester. J Am Chem Soc 113:5775–5783CrossRefGoogle Scholar
  28. 28.
    Koester DC, Leibeling M, Neufeld R, Werz DB (2010) A Pd-catalyzed approach to (1 → 6)-linked C-glycosides. Org Lett 12:3934–3937CrossRefGoogle Scholar
  29. 29.
    Abas A, Beddoes RL, Conway JC, Quayle P, Urch CJ (1995) Synthesis and diels-alder reactions of semicyclic sugar containing dienes. Synlett 1995:1264–1266CrossRefGoogle Scholar
  30. 30.
    Johns BA, Pan YT, Elbein AD, Johnson CR (1997) Synthesis and Biological Evaluation of Aza-C-disaccharides: (1→6), (1→4), and (1→1) Linked Sugar Mimics J Am Chem Soc 119:4856–4865Google Scholar
  31. 31.
    Kometani T, Kondo H, Fujimori Y (1988) Improvement in O → C-glycoside rearrangement approach to C-aryl glycosides: use of 1-O-acetyl sugar as stable but efficient glycosyl donor. Synthesis 1988:1005–1007CrossRefGoogle Scholar
  32. 32.
    Burkhart F, Hoffmann M, Kessler H (1997) Synthesis of a C-glycosidic analog of N-glucoasparagine. Angew Chem Int Ed 36:1191–1192CrossRefGoogle Scholar
  33. 33.
    Parker KA, Coburn CA (1991) Reductive aromatization of quinol ketals: a new synthesis of C-aryl glycosides. J Am Chem Soc 113:8516–8518CrossRefGoogle Scholar
  34. 34.
    Martin OR, Lai W (1993) Synthesis and conformational studies of beta-(1.fwdarw.6)- and beta, beta-(1.fwdarw.1)-linked C-disaccharides. J Org Chem 58:176–185CrossRefGoogle Scholar
  35. 35.
    Schawab P, France MB, Ziller JW, Grubbs RH (1995) A series of well-defined metathesis catalysts - synthesis of [RuCl2(=CHR′)(PR3)2] and its reactions. Angew Chem Int Ed 34:2039–2041CrossRefGoogle Scholar
  36. 36.
    Postema MHD, Piper JL, Betts RL (2005) RCM-based synthesis of a variety of β-C-glycosides and their in vitro anti-solid tumor activity. J Org Chem 70:829–836CrossRefGoogle Scholar
  37. 37.
    Roy R, Dominique R, Das SK (1999) Extended alkenyl glycosides by ruthenium-catalyzed cross-metathesis reaction and application toward novel C-linked pseudodisaccharides. J Org Chem 64:5408–5412CrossRefGoogle Scholar
  38. 38.
    Mazéas T, Skrydstrup JM, Beau JM (1995) Synthesis of an RGD-Sialyl-LewisX glycoconjugate: a new highly active ligand for P-selectin. Angew Chem Int Ed 107:990–993CrossRefGoogle Scholar
  39. 39.
    Krintel SL, Jiménez-Barbero J, Skrydstrup T (1999) A convergent synthesis of alpha-C-1,3-mannobioside via SmI2-promoted C-glycosylation. Tetrahedron Lett 40:7565–7568CrossRefGoogle Scholar
  40. 40.
    Dondoni A, Marra A (2000) Methods for anomeric carbon-linked and fused sugar amino acid synthesis: the gateway to artificial glycopeptides. Chem Rev 100:4395–4422CrossRefGoogle Scholar
  41. 41.
    Ohnishi Y, Ichikawa Y (2002) Stereoselective synthesis of a C-glycoside analogue of N-Fmoc-serine beta-N-acetylglucosaminide by Ramberg-Bäcklund rearrangement. Bioorg Med Chem Lett 12:997–999CrossRefGoogle Scholar
  42. 42.
    Yang G, Franck RW, Bittman R, Samadder P, Arthur G (2001) Synthesis and growth inhibitory properties of glucosamine-derived glycerolipids. Org Lett 3:197–200CrossRefGoogle Scholar
  43. 43.
    Griffin FK, Paterson DE, Taylor RJ (1999) Ramberg-Bäcklund approaches to the synthesis of C-linked disaccharides. Angew Chem Int Ed 38:2939–2942CrossRefGoogle Scholar
  44. 44.
    Togo H, He W, Waki Y, Yokohama M (1998) C-glycosidation technology with free radical reactions. Synlett 1998(7):700–717CrossRefGoogle Scholar
  45. 45.
    Chenede A, Perrin E, Rekai ED, Sinaÿ P (1994) Synthesis of C-disaccharides by a samarium diiodide induced intramolecular coupling reaction of tethered sugars. Synlett 1994:420–422CrossRefGoogle Scholar
  46. 46.
    Giese B, Gröninger KS, Witzel T, Korth HG, Sustmann R (1987) Synthesis of 2-deoxy sugars. Angew Chem Int Ed 26:233–234CrossRefGoogle Scholar
  47. 47.
    Taillefumier C, Chapleur Y (2004) Synthesis and uses of exo-glycals. Chem Rev 104:263–292CrossRefGoogle Scholar
  48. 48.
    Bischofberger K, Hall RH, Jordaan A (1975) Synthesis of glycosyl-amino acids. J Chem Soc Chem Commun 806–807Google Scholar
  49. 49.
    Hall RH, Bischofberger K, Eitelman SJ, Jordann A (1977) Synthesis of C-glycosyl compounds. Part 1. Reaction of ethyl isocyanoacetate with 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone. J Chem Soc Perkin 1 743–753Google Scholar
  50. 50.
    Chapleur Y (1984) A convenient synthesis of substituted chiral tetrahydrofurans from sugar γ-lactones. J Chem Soc Chem Commun 449–450Google Scholar
  51. 51.
    Wilcox CS, Long GW, Suh H (1984) A new approach to C-glycoside congeners: metal carbenemediated methylenation of aldonolactones. Tetrahedron Lett 25:395–398CrossRefGoogle Scholar
  52. 52.
    Brockhaus M, Lehmann J (1977) The conversion of 2,6-anhydro-1-deoxy-d-galacto-hept-1-enitol into 1-deoxy-d-galacto-heptulose by β-d-galactosidase. Carbohydr Res 53:21–31CrossRefGoogle Scholar
  53. 53.
    Eitelman SJ, Hall RH, Jordaan AJ (1976) Synthesis of acyclic sugar oxazoles. J Chem Soc Chem Commun 923–924Google Scholar
  54. 54.
    Griffin FK, Paterson DE, Murphy PV, Taylor RJK (2002) A new route to exo-glycals using the Ramberg-Backlund rearrangement. Eur J Org Chem 2002:1305–1323CrossRefGoogle Scholar
  55. 55.
    Toth M, Somsak L (2001) exo-Glycals from glycosyl cyanides. First generation of C-glycosylmethylene carbenes from 2,5-and 2,6-anhydroaldose tosylhydrazones. J Chem Soc Perkin 1 942–943Google Scholar
  56. 56.
    Lay L, Nicotra F, Panza L, Russo G, Caneva E (1992) Synthesis of C-disaccharides through dimerization of exo-enitols. J Org Chem 57:1304–1306CrossRefGoogle Scholar
  57. 57.
    Li X, Takahasi H, Ohtake H, Ikegami S (2004) 1,3-Dipolar cycloaddition of exo-methylenesugars with nitrone: approach to new amino-C-ketosyl disaccharides. Tetrahedron Lett 45:4123–4126CrossRefGoogle Scholar
  58. 58.
    Casiraghi G, Zanardi F, Rassu G, Spanu P (1995) Stereoselective approaches to bioactive carbohydrates and alkaloids - with a focus on recent syntheses drawing from the chiral pool. Chem Rev 95:1677CrossRefGoogle Scholar
  59. 59.
    Vauzeilles B, Cravo D, Mallet J-M, Sinay P (1993) An expeditious synthesis of a c-disaccharide using a temporary ketal connection. Synlett 1993:522–524CrossRefGoogle Scholar
  60. 60.
    Fairbanks AJ, Perrin E, Sinaÿ P (1996) Synthesis of the carbon skeleton of the herbicidins via a temporary silaketal tether. Synlett 1996:679–681CrossRefGoogle Scholar
  61. 61.
    Mazeas DST, Doumeix O, Beau JM (1994) Samarium iodide induced intramolecular C-glycoside formation: efficient radical formation in the absence of an additive. Angew Chem Int Ed 33:1383–1386CrossRefGoogle Scholar
  62. 62.
    Feng W, Fang Z, Yang J, Zheng B, Jiang Y (2011) Microwave-assisted efficient synthesis of aryl ketone β-C-glycosides from unprotected aldoses. Carbohydr Res 346:352–356CrossRefGoogle Scholar
  63. 63.
    Sato S, Koide T (2010) Synthesis of vicenin-1 and 3, 6,8- and 8,6-di-C-β-D-(glucopyranosyl-xylopyranosyl)-4′,5,7-trihydroxyflavones using two direct C-glycosylations of naringenin and phloroacetophenone with unprotected D-glucose and D-xylose in aqueous solution as the key reactions. Carbohydr Res 345:1825–1830CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Marco Brito-Arias
    • 1
  1. 1.Unidad Profesional Interdisciplinaria de Biotecnología Instituto Politécnico Nacional (UPIBI-IPN) Avenida Acueducto s/n Colonia La Laguna TicománCiudad de MéxicoMéxico

Personalised recommendations