Download PDF
Synlett 2011(8): 1160-1164  
DOI: 10.1055/s-0030-1259958
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

N,N′-Carbonyldiimidazole-Mediated DBU-Catalyzed One-Pot Synthesis of Urea-Tethered Glycosyl Amino Acids and Glycoconjugates

V. V. Sureshbabu*, Basavaprabhu
Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Dr. B. R. Ambedkar Veedhi, Bangalore University, Bangalore, 560 001, India
e-Mail: hariccb@hotmail.com; e-Mail: sureshbabuvommina@rediffmail.com; e-Mail: hariccb@gmail.com;
Further Information

Publication History

Received 8 November 2010
Publication Date:
18 April 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient, mild, simple, and alternative one-pot protocol for the synthesis of urea-tethered glycosyl amino acids mediated by N,N′-carbonyldiimidazole employing DBU as a catalyst is described. This protocol is also extended for the synthesis of urea-tethered disaccharides and oligosaccharides.

Key words

urea-tethered glycoconjugates - N,N′-carbonyldiimidazole - DBU - base catalysis

    References and Notes

  • 1 Varki A. Glycobiology  1993,  3:  97 
    CrossrefPubMedGoogle Scholar
  • 2a Dwek RA. Chem. Rev.  1996,  96:  683 
    Google Scholar
  • 2b Selvador LA. Eloffson M. Kihlberg J. Tetrahedron  1995,  51:  5643 
    Google Scholar
  • 2c Taylor CM. Tetrahedron  1998,  54:  11317 
    Google Scholar
  • 2d Davis BG. Chem. Rev.  2002,  102:  579 
    Google Scholar
  • 3 Kunz H. Angew. Chem., Int. Ed. Engl.  1987,  26:  294 
    CrossrefGoogle Scholar
  • 4 Marcaurelle LA. Bertozzi CR. Chem. Eur. J.  1999,  5:  1384 
    CrossrefGoogle Scholar
  • 5a Cassarco MR. Brown RT. J. Org. Chem.  2003,  68:  8853 
    Google Scholar
  • 5b McDonald FE. Danishefsky SJ. J. Org. Chem.  1992,  57:  7001 
    Google Scholar
  • 5c Khorlin AY. Zurabyan SE. Macharadze RG. Carbohydr. Res.  1980,  85:  201 
    Google Scholar
  • 5d Gustafson GL. Gander JE. Methods Enzymol.  1984,  107:  172 
    Google Scholar
  • 5e Kuijpers BHM. Groothuys S. Keereweer A. Quaedflieg PJLM. Blaauw RH. Delft FLV. Rutjes FPJT. Org. Lett.  2004,  6:  3123 
    Google Scholar
  • 5f Synthesis of Peptides and Peptidomimetics (Houben-Weyl)   Vol. E22c:  Goodman M. Felix A. Moroder L. Toniolo C. Thieme; Stuttgart: 2003. 
    Google Scholar
  • 5g Cho CY. Youngquist RS. Paikoff SJ. Beresini MH. Hebert AR. Berleau LT. Liu CW. Wemmer DE. Keough T. Schultz PG.
    J. Am. Chem. Soc.  1998,  120:  7706 
    Google Scholar
  • 6a Choi KH. Hamilton AD. Coord. Chem. Rev.  2003,  240:  101 
    Google Scholar
  • 6b Castellano RK. Nuckolls C. Rebek J.
    J. Am. Chem. Soc.  1999,  121:  11156 
    Google Scholar
  • 6c Cho YL. Rudkevich DM. Shivanyuk A. Rissanen K. Rebek J. Chem. Eur. J.  2000,  6:  3788 
    Google Scholar
  • 7a Avalos M. Babiano R. Cintas P. Jimenez J. Palacios JC. Valencia C. Tetrahedron  1993,  49:  2655 
    Google Scholar
  • 7b Avalos M. Babiano R. Cintas P. Jimenez J. Palacios JC. Valencia C. Tetrahedron  1993,  49:  2676 
    Google Scholar
  • 7c Maya I. Lopez O. Maza S. Fernandez-Bolanos JG. Fuentes J. Tetrahedron Lett.  2003,  44:  8539 
    Google Scholar
  • 8 Nishiyama T. Ichikawa Y. Isobe M. Synlett  2003,  47 
    Google Scholar
  • 9 Park NH. Nguyen HM. Org. Lett.  2009,  11:  2433 
    CrossrefGoogle Scholar
  • 10a Kovacs J. Pinter I. Messmer A. Toth G. Duddek H. Carbohydr. Res.  1987,  166:  101 
    Google Scholar
  • 10b Diaz VM. Ortiz C. Fuentes J. Garcia JM. Carbohydr. Res.  1987,  166:  161 
    Google Scholar
  • 11 Ichikawa Y. Nishiyama T. Isobe M. Synlett  2000,  1253 
    Article in Thieme ConnectGoogle Scholar
  • 12a Ichikawa Y. Matsukawa Y. Nishiyama T. Isobe M. Eur. J. Org. Chem.  2004,  69:  586 
    Google Scholar
  • 12b Ichikawa Y. Nishiyama T. Isobe M. J. Org. Chem.  2001,  66:  4200 
    Google Scholar
  • 12c Ukita C. Hamada A. Yoshida M. Chem. Pharm. Bull.  1964,  12:  454 
    Google Scholar
  • 12d Fischer E. Ber. Dtsch. Chem. Ges.  1914,  47:  1377 
    Google Scholar
  • 12e Johnson TB. Bergmann W. J. Am. Chem. Soc.  1932,  54:  3360 
    Google Scholar
  • 12f Bannister B. J. Antibiot.  1972,  25:  377 
    Google Scholar
  • 12g Pinter I. Kovacs J. Toth G. Carbohydr. Res.  1995,  273:  99 
    Google Scholar
  • 13a Shioiri T. Ninomiya K. Yamada S. J. Am. Chem. Soc.  1972,  94:  6203 
    Google Scholar
  • 13b Sawada D. Sasayama S. Takahashi H. Ikegami S. Tetrahedron Lett.  2006,  47:  7219 
    Google Scholar
  • 14a Dolle RE. J. Comb. Chem.  2001,  3:  477 
    Google Scholar
  • 14b Dolle RE. J. Comb. Chem.  2000,  2:  383 
    Google Scholar
  • 15a Hemantha HP. Chennakrishnareddy G. Vishwanatha TM. Sureshbabu VV. Synlett  2009,  407 
    Google Scholar
  • 15b Sureshbabu VV. Chennakrishnareddy G. Hemantha HP. Synlett  2010,  715 
    Google Scholar
  • 16a Sharma RK. Synlett  2007,  3073 ; and references cited therein
    Google Scholar
  • 16b Zang X. Rodrigues J. Evans L. Hinkle B. Ballantyne L. Pena M. J. Org. Chem.  1997,  62:  6420 
    Google Scholar
  • 16c Fustero S. Torre MG. Sanz-Cervera JF. Arellano CR. Piera J. Simn A. Org. Lett.  2002,  4. 3651 
    Google Scholar
  • 16d Figueiredo RM. Fröhlich R. Christmann M. J. Org. Chem.  2006,  71:  4147 
    Google Scholar
  • 16e Weber AL. Orig. Life Evol. Biosph.  2005,  35:  421 
    Google Scholar
  • 16f Dawson PE. Muir TW. Clark-Lewis I. Kent SBH. Science  1994,  266:  776 
    Google Scholar
  • 16g Dubé P. Fine Nathel NF. Vetelino M. Couturier M. Aboussafy CL. Pichette S. Jorgensen ML. Hardink M. Org. Lett.  2009,  11:  5622 
    Google Scholar
  • 16h Opatz T. Kallus C. Wunberg T. Kunz H. Tetrahedron  2004,  60:  8613 
    Google Scholar
  • 16i Ford MJ. Ley SV. Synlett  1990,  255 
    Google Scholar
  • 17 Oakenfull DG. Salvesen K. Jencks WP. J. Am. Chem. Soc.  1971,  93:  188 
    CrossrefGoogle Scholar
  • 18 Larrivee-Aboussafy C. Jones BP. Price KE. Hardink MA. McLaughlin RW. Lillie BM. Hawkins JM. Vaidyanathan R. Org. Lett.  2010,  12:  324 
    CrossrefGoogle Scholar
  • 19 Dobashi K. Nagaoka K. Watanabe Y. Nishida M. Hamada M. Takeuchi T. Umezawa H. J. Antibiot.  1985,  1166 
    Google Scholar
20

The epimerization study was carried out by ¹H NMR and HPLC analyses of the glycosyl ureas 3k and 3l synthesized by the protocol described below.
Glucosamine (2a),was converted into two epimeric glycosyl ureas 3k and 3l as outlined in Scheme  [³] by coupling separately with l-Ala-OMe (1k) and d-Ala-OMe (1l), respectively. An equimolar mixture of these two epimers was obtained by coupling with the racemic mixture of l- and d-Ala-OMe. The ¹H NMR spectrum of 3k and 3l contained distinct methyl group doublets at δ = 1.52, 1.54 ppm and δ = 1.55, 1.58 ppm, respectively; whereas the epimeric mixture showed CH3 group signals at δ = 1.51, 1.54 ppm and δ = 1.56, 1.59 ppm corresponding to two doublets. Additionally, HPLC analysis of the pure l- and d-Ala-OMe-derived glycosyl ureas 3k and 3l showed single peaks at different
t R values i.e., t R = 9.23 and t R = 9.61 (method: gradient 0.1% TFA H2O-MeCN; MeCN 30-100% in 30 min), respectively.

21

General Procedure for the Preparation of 3a-f
To a suspension of N,N′-carbonyldiimidazole (1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added amino acid ester (1.0 mmol) and DBU (0.2 mmol), and the reaction mixture was stirred at ambient temperature for 6-7 min. The glycosyl amine (1.0 mmol) and DBU (0.3 mmol) was then added at 0 ˚C, and the resulting mixture was stirred for about 3 h at 0 ˚C. After completion of the reaction, the resulting solution was diluted with CH2Cl2 (10 mL) and washed with citric acid (2 × 10 mL), H2O (2 × 10 mL), and brine (10 mL). The organic layer was dried over anhyd Na2SO4, filtered, and evaporated to obtain the crude product. Pure urea-tethered glycoconjugate was obtained as a solid on column chromatography eluting with EtOAc-hexane (4:6).
The procedure followed for the synthesis of 3g-j is similar to that described above with the only difference being the use of 0.6 mmol DBU during the addition of the second amine component.
Spectroscopic Data for Compound 3a White solid. IR (KBr): νmax = 3385, 1748, 1655, 1560, 1231 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.07 (s, 3 H), 3.06 (d, 2 H), 3.69 (s, 3 H), 3.77 (ddd, J = 10.0, 4.3, 2.1 Hz, 1 H), 4.10 (dd, J = 12.3, 1.8 Hz, 1 H), 4.29 (dd, J = 12.3, 4.6 Hz, 1 H), 4.71 (q, J = 7.0 Hz, 6.0 Hz, 1 H), 4.88 (t, J = 9.6 Hz, 1 H), 5.10 (t, J = 9.4 Hz, 1 H), 5.15 (t, J = 9.3 Hz, 1 H), 5.12-5.22 (br, 1 H), 5.33 (d, J = 9.6 Hz, 1 H), 5.40-5.53 (br, 1 H), 7.04-7.16 (m, 2 H), 7.22- 7.35 (m, 3 H) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 21.0, 21.2, 38.0, 53.1, 54.5, 62.6, 69.5, 70.2, 73.2, 74.3, 81.6, 128.4, 129.1, 130.3, 136.8, 156.5, 169.8, 170.1, 171.0, 171.6, 173.8 ppm.
Spectroscopic Data for Compound 3h White solid. IR (KBr): νmax = 1669, 1558, 1229 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.31 (s, 3 H), 1.49 (s, 3 H), 2.00 (s, 3 H), 2.02 (s, 3 H), 2.06 (s, 3 H), 2.09 (s, 3 H), 2.14 (s, 3 H), 3.32 (dd, J = 14.6, 5.8 Hz, 1 H), 3.41 (s, 3 H), 3.52 (ddd, J = 15.0, 5.8, 2.6 Hz, 1 H), 3.78 (ddd, J = 10.8, 5.6, 2.4 Hz, 1 H), 3.86 (ddd, J = 10.0, 4.2, 2.2 Hz, 1 H), 4.18 (dd, J = 12.6, 2.0 Hz, 1 H), 4.20 (d, J = 5.8 Hz, 1 H), 4.24 (dd, J = 7.6, 5.5 Hz, 1 H), 4.35 (dd, J = 12.6, 4.0 Hz, 1 H), 4.90 (dd, J = 10.5, 7.5 Hz, 1 H), 4.93 (t, J = 9.5 Hz, 1 H), 4.97 (s, 1 H), 5.12 (t, J = 6.0 Hz, 1 H), 5.15 (t, J = 9.7 Hz, 1 H), 5.19 (t, J = 9.4 Hz, 1 H), 5.36 (t, J = 9.4 Hz, 1 H), 5.47 (br d, J = 9.5 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 20.9, 21.5, 21.9, 26.8, 27.9, 42.4, 57.3, 63.9, 68.6, 70.5, 72.1, 73.3, 75.8, 76.7, 77.9, 82.1, 99.6, 110.8, 158.2, 170.4, 170.9, 172.0, 173.9, 174.5 ppm.