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Synlett 2004(9): 1529-1532  
DOI: 10.1055/s-2004-829074
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Novel Pseudodisaccharides and Neoglycoconjugates Containing an N-Glycosyl Carbamate Backbone

Davide Prosperi*a,b, Silvia Ronchi, Luigi Panza, Anna Rencurosia, Giovanni Russob
a Istituto di Scienze e Tecnologie Molecolari (ISTM) - CNR, via Golgi 19, 20133 Milano, Italy
b Dipartimento di Chimica Organica e Industriale, Centro Interdisciplinare Studi Bio-molecolari e Applicazioni Industriali (CISI), Università degli Studi di Milano, via Venezian 21, 20133 Milano, Italy
Fax: +39(02503)14061; e-Mail: davide.prosperi@unimi.it;
Further Information

Publication History

Received 17 March 2004
Publication Date:
29 June 2004 (online)

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Abstract

A new class of pseudodisaccharides is presented in which a N-glycosyl carbamate is connected to a monosaccharide unit, using a mild and stereo-controlled isocyanide approach. The methodology was extended to the case of neoglycoconjugates ­useful as synthons for the construction of molecules with potential therapeutic interest.

Key words

carbohydrates - glycosyl carbamates - oligosaccharides - isocyanate - glycoconjugates

    References

  • 1a Varki A. Glycobiology  1993,  3:  97 
    Google Scholar
  • 1b Dwek AR. Chem. Rev.  1996,  96:  683 
    Google Scholar
  • 1c Reitter JN. Means RE. Desrosiers RC. Nat. Med.  1998,  4:  679 
    Google Scholar
  • 1d Brocke C. Kunz H. Bioorg. Med. Chem.  2002,  10:  3085 
    Google Scholar
  • 1e Jennings HJ. Adv. Carbohydr. Chem. Biochem.  1983,  41:  155 
    Google Scholar
  • 2 Pigman W. The Carbohydrates, Chem. Biochem., Part II A   Horton D. Academic Press; New York: 1970.  p.242 
    Google Scholar
  • 3a García Fernández JM. Ortiz Mellet C. Diáz Peréz VM. Jimenez Blanco JL. Fuentes J. Tetrahedron  1996,  52:  12947 
    CrossrefGoogle Scholar
  • 3b Lay L. Panza L. Poletti L. Prosperi D. Russo G. Tetrahedron  2000,  56:  4811 
    CrossrefGoogle Scholar
  • 3c García-Moreno MI. Benito JM. Ortiz Mellet C. García Fernández JM. Tetrahedron: Asymmetry  2000,  11:  1331 
    CrossrefGoogle Scholar
  • 4a Ogawa T. Nakabayashi S. Shibata S. Agric. Biol. Chem.  1983,  47:  281 
    CrossrefGoogle Scholar
  • 4b Ichikawa Y. Nishiyama T. Isobe M. J. Org. Chem.  2001,  66:  4200 
    CrossrefGoogle Scholar
  • 5 Ichikawa Y. Matsukawa Y. Nishiyama T. Isobe M. Eur. J. Org. Chem.  2004,  586 
    CrossrefGoogle Scholar
  • 6a Ichikawa Y. Nishiyama T. Isobe M. Synlett  2000,  1253 
    Google Scholar
  • 6b Nishiyama T. Ichikawa Y. Isobe M. Synlett  2003,  47 
    Google Scholar
  • 7 Prosperi D. Ronchi S. Lay L. Rencurosi A. Russo G. Eur. J. Org. Chem.  2004,  395 
    CrossrefGoogle Scholar
  • 8 Toth G. Pintér I. Kovács J. Haessner R. Magn. Reson. Chem.  1997,  37:  203 
    Google Scholar
  • 10 Petrakova E. Glaudemans CPJ. Carbohydr. Res.  1995,  279:  133 
    CrossrefGoogle Scholar
  • 11 Toepfer A. Schmidt RR. J. Carbohydr. Chem.  1993,  12:  809 
    Google Scholar
  • 12a

    Procedure for the Deprotection of 1a: Compound 1a (90 mg, 0.11 mmol) was hydrogenated in MeOH (2 mL) in the presence of a catalytic amount of Pd/C; the crude product was deacetylated in methanolic NaOMe (0.02 mmol), giving 44 mg of 4a, with a 100% overall yield.

  • 12b

    Deprotection of 1d: To a solution of compound 1d (109 mg, 0.13 mmol) in CH2Cl2 (2 mL), 90% aq TFA (620 µL) was added; after 1.5 h, the mixture was diluted with CH2Cl2 (15 mL) and washed with a sat. solution of NaHCO3 (10 mL). The organic layer was dried over Na2SO4 and the solvent was evaporated. The crude product was dissolved in dry MeOH (4 mL) and 70 µL of a 1 M solution of NaOMe (0.07 mmol) were added, furnishing 60 mg of 4d (92%) as a white solid after flash chromatography.

  • 13 Chaxiraxi N. Vazquéz JT. Tetrahedron: Asymmetry  2003,  14:  2793 
    CrossrefGoogle Scholar
  • 14 García Fernández JM. Ortiz Mellet C. Sulfur Rep.  1996,  19:  61 
    CrossrefGoogle Scholar
  • 15 Soloway AH. Tjarks W. Barnum BA. Rong F.-G. Barth RF. Codogni IM. Wilson JG. Chem. Rev.  1998,  98:  1515 
    CrossrefPubMedGoogle Scholar
  • 16a Locher GL. Am. J. Roentgenol.  1936,  36:  1 
    CrossrefGoogle Scholar
  • 16b Hawthorne MF. Angew. Chem., Int. Ed. Engl.  1993,  32:  950 
    CrossrefGoogle Scholar
  • 17 Endo Y. Yamamoto K. Kagechika H. Bioorg. Med. Chem. Lett.  2003,  13:  4089 ; and references cited therein
    CrossrefGoogle Scholar
  • 18a Tietze LF. Bothe U. Chem.-Eur. J.  1998,  4:  1179 
    Google Scholar
  • 18b Tietze LF. Bothe U. Griesbach U. Nakaichi M. Hasegawa T. Nakamura H. Yamamoto Y. Bioorg. Med. Chem.  2001,  9:  1747 
    Google Scholar
  • 18c Giovenzana GB. Lay L. Monti D. Palmisano G. Panza L. Tetrahedron  1999,  55:  14123 
    Google Scholar
  • 18d Maurer JL. Berchier F. Serino AJ. Knobler CB. Hawthorne MF. J. Org. Chem.  1990,  55:  838 
    Google Scholar
  • 19 Nakamura H. Aoyagi K. Yamamoto Y. J. Am. Chem. Soc.  1998,  120:  1167 
    CrossrefGoogle Scholar
9

Selected data for compound 1a. Mp 63-65 °C; [α]D 23 +14.1 (c 1.00, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 1.94 (3 H, s, OAc), 2.01 (3 H, s, OAc), 2.02 (3 H, s, OAc), 2.07 (3 H, s, OAc), 3.35 (3 H, s, OMe), 3.41 (1 H, dd, J = 9.6, 1.5 Hz, H-6a), 3.51 (1 H, dd, J = 9.6, 3.4 Hz, H-6b), 3.72-3.86 (2 H, m, H-5, H-5′), 3.99 (1 H, t, J = 9.2 Hz, H-3), 4.07 (1 H, dd, J = 12.6, 1.1 Hz, H-6a′), 4.19-4.37 (2 H, m, H-4, H-6b′), 4.48-5.13 (9 H, m, H-1, H-2′, H-4′, 3 CH2Ph), 5.01 (1 H, d, J = 8.9 Hz, H-1′), 5.29 (1 H, t, J = 9.3 Hz, H-3′), 5.63 (1 H, br d, J = 9.5 Hz, NH), 7.20-7.41 (15 H, m, Ph). 13C NMR (50 MHz, CDCl3): δ = 20.5, 55.2, 61.5, 64.4, 68.0, 68.6, 70.2, 72.7, 73.2, 73.4, 75.0, 75.7, 77.6, 79.8, 80.7, 81.8, 97.9, 127.6, 127.9, 128.1, 128.4, 137.8, 137.9, 138.5, 155.2, 169.5, 169.9, 170.5.

20

Selected data for Compound 11: [α]D 21 +40.1 (c 1.00, MeOH). 1H NMR (300 MHz, CD3OD): δ = 1.11-3.16 (10 H, m, BH), 3.45 (1 H, ddd, J = 9.0, 4.8, 3.1 Hz, H-5), 3.66 (1 H, t, J = 9.0 Hz, H-4), 3.70-3.77 (3 H, m, H-3, H-6a, H-6b), 3.80, (1 H, dd, J = 2.8, 1.8 Hz, H-2), 4.58 (1 H, br s, carboranyl CH), 4.63 (2 H, s, CH2), 5.26 (1 H, d, J = 1.8 Hz, H-1). 13C NMR (75 MHz, CD3OD): δ = 63.0, 66.4, 69.0, 72.0, 72.5, 76.1, 82.6, 156.8.