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Synlett 2003(9): 1291-1294
DOI: 10.1055/s-2003-40342
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Fluorine-Containing Core-2 Tetrasaccharides

Jie Xia, James L. Alderfer, Conrad F. Piskorz, Robert D. Locke, Khushi L. Matta*
Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
Fax: +1(716)8453458; e-Mail: khushi.matta@roswellpark.org;
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Publication History

Received 31 March 2003
Publication Date:
30 June 2003 (online)

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Abstract

Synthesis of core-2 branched tetrasaccharides 1-3, in which a fluorine atom was substituted at the 3 or 4-position of galactose residues is described. Glycosyl imidates 13, and 19 were prepared and used to provide novel glycosyl disaccharide donors 15 and 21, respectively. Coupling of acceptor 7 with glycosyl bromide 6 provides a disaccharide that was further converted into disaccharide acceptor 8. The coupling of acceptor 14 with donor 13, and acceptor 20 with donor 19 provided disaccharides that were converted to disaccharide donors 15 and 21, respectively. Regioselective glycosylation of acceptors 8, and 16 with donors 9, 15, and 21 provided tetrasaccharides 10, 17, and 22 respectively, which were systematically deprotected to targets 1-3.

Key words

tetrasaccharides - galactose residues - core-2 O-linked glycoproteins

    References

  • 1a Capon C. Laboisse CL. Wieruszrski J.-M. Maoret JJ. Auheron C. Fournet B. J. Biol. Chem.  1992,  267:  19248 
    CrossrefPubMedSearch in Google Scholar
  • 1b Capon C. Wieruszeski J.-M. Lemoine J. Byrd JC. Leffler H. Kim YS. J. Biol. Chem.  1997,  272:  31957 
    CrossrefPubMedSearch in Google Scholar
  • 1c Brockhausen I. Biochem. Biophys. Acta  1999,  1473:  67 
    CrossrefPubMedSearch in Google Scholar
  • 1d Rosen SD. Bertozzi CR. Curr. Opin. Cell Biol.  1994,  6:  663 
    CrossrefPubMedSearch in Google Scholar
  • 1e Brocke C. Kunz H. Bioorg. Med. Chem.  2002,  10:  3085 
    CrossrefPubMedSearch in Google Scholar
  • 2a Dwek RA. Chem. Rev.  1996,  96:  683 
    CrossrefPubMedSearch in Google Scholar
  • 2b Lee YC. Lee TR. Acc. Chem. Res.  1995,  28:  321 
    CrossrefPubMedSearch in Google Scholar
  • 2c Varki A. Glycobiology  1993,  3:  97 
    CrossrefPubMedSearch in Google Scholar
  • 3a Nicolaou KC. Mitchell HJ. Angew. Chem. Int. Ed.  2001,  40:  1576 
    Search in Google Scholar
  • 3b Sanders WJ. Manning DD. Koeller KM. Kiessling LL. Tetrahedron  1997,  53:  16391 
    Search in Google Scholar
  • 3c Wong C.-H. Acc. Chem. Res.  1999,  32:  376 
    Search in Google Scholar
  • 3d Gege C. Vogel J. Bendas G. Rothe U. Schmidt RR. Chem.-Eur. J.  2000,  6:  111 
    Search in Google Scholar
  • 3e Herzner H. Reipen T. Schultz M. Kunz H. Chem. Rev.  2000,  100:  4495 
    Search in Google Scholar
  • 3f Lergenmuler M. Ito Y. Ogawa T. Tetrahedron  1998,  54:  1381 
    Search in Google Scholar
  • 3g Kanie O. Barresi A. Ding Y. Otter Y. Forsberg LS. Ernst B. Hindsgaul O. Angew. Chem., Int. Ed. Engl.  1995,  34:  2720 
    Search in Google Scholar
  • 3h Jain RK. Huang B.-G. Chandrasekaran EV. Matta KL. Chem. Commun.  1997,  23 
  • 3i Huang B.-G. Jain RK. Locke RD. Alderfer JL. Tabaczynski WA. Matta KL. Tetrahedron Lett.  2000,  41:  6279 
    Search in Google Scholar
  • 3j Xia J. Alderfer JL. Piskorz CF. Matta KL. Chem.-Eur. J.  2000,  6:  3442 
    Search in Google Scholar
  • 3k Xia J. Alderfer JL. Piskorz CF. Matta KL. Chem.-Eur. J.  2001,  7:  356 
    Search in Google Scholar
  • 4a O’Hagan D. Rzepa HS. Chem. Commun.  1997,  645 
  • 4b Howard JAK. Hoy VJ. O’Hagan D. Smith GT. Tetrahedron  1996,  53:  12613 
    Search in Google Scholar
  • 5a Sarkar AK. Rostand KS. Jain RK. Matta KL. Esko JD. J. Biol. Chem.  1997,  272:  25608 
    CrossrefSearch in Google Scholar
  • 5b Woynarowska B. Skrincosky DM. Haag A. Sharma M. Matta KL. Bernacki RJ. J. Biol. Chem.  1994,  269:  22797 
    CrossrefSearch in Google Scholar
  • 5c Sarkar AK. Fritz TA. Taylor WH. Esko JD. Proc. Natl. Acad. Sci. USA  1995,  92:  3323 
    CrossrefSearch in Google Scholar
  • 5d Goon S. Bertozzi CR. J. Carbohydr. Chem.  2002,  21:  943 
    CrossrefSearch in Google Scholar
  • 6 Card PJ. Reddy CS. J. Org. Chem.  1983,  48:  4734 
    CrossrefSearch in Google Scholar
  • 7 Kovac P. Yeh HJ. Glaudemans CP. Carbohydr. Res.  1985,  140:  277 
    CrossrefSearch in Google Scholar
  • 8 Jain RK. Piskorz CF. Chandrasekaran EV. Matta KL. Carbohydr. Res.  1995,  271:  247 
    Search in Google Scholar
  • 9a Koch K. Chambers RJ. Carbohydr. Res.  1993,  241:  295 
    CrossrefSearch in Google Scholar
  • 9b Dax K. Albert M. Ortner J. Paul BJ. Carbohydr. Res.  2000,  327:  47 
    CrossrefSearch in Google Scholar
  • 10 Physical data: Compound 1: Rf = 0.5 (i-C3H9OH-HOAc-H2O, 3:1:1); 1H NMR (D2O, DQF-COSY and ROESY, 400 MHz): δ = 7.50-7.20 (m, 5 H, ArH), 4.99 (d, 1 H, J 1,2 = 3.4 Hz, HA-1), 4.72 (d, 1 H, J gem = 12.6 Hz, PhCHAO, ABq), 4.61 (dq, 1 H, HB-3), 4.58 (d, 1 H, J 1,2 = 7.6 Hz, HB-1), 4.53 (d, 1 H, J gem = 12.4 Hz, PhCHBO, ABq), 4.49 (d, 1 H, J 1,2 = 8.6 Hz, HC-1), 4.48 (d, 1 H, J 1,2 = 7.6 Hz, HD-1), 4.35 (dd, 1 H, HA-2), 4.23 (d, 1 H, J = 2.8 Hz, HA-4), 4.20 (dd, 1 H, HB-4), 4.15 (dd, 1 H, HA-5), 4.07 (dd, 1 H, HA-6b), 4.04 (dd, 1 H, HA-3), 4.01 (dd, 1 H), 3.94 (d, 1 H, J = 2.7 Hz, HD-4), 3.90-3.50 (m, 15 H, HB-2, HD-2), 2.31 (s, 3 H, Ac), 2.21 (s, 3 H, Ac); 13C NMR (D2O, 100.6 MHz): δ = 175.76 (C=O), 175.52 (C=O), 138.24, 130.07, 129.96, 129.71, 105.12 (d, 3 J C-F = 11.3 Hz), 104.21, 102.76, 97.62, 94.10 (d, 1 J C-F = 183.4 Hz), 79.90, 78.48, 76.65, 76.06, 75.02, 74.96, 73.84, 73.80, 72.27, 70.91, 70.86, 70.77, 70.59 (d, 2 J C-F = 18.6 Hz), 69.97 (d, 2 J C-F = 20.4 Hz), 62.31, 61.94, 61.89, 61.40, 56.39, 49.83, 23.58 (NAc), 23.25 (NAc). ESIMS (negative mode) Calcd for C35H53O20N2F (m/z)[M = 840]. Found: 839.5[M]-, 875.5 [M + Cl]-. Compound 2: 1 H NMR (D2O, DQF-COSY, TOCSY and ROESY, 400 MHz): δ = 7.50-7.00 (m, 5 H, ArH), 5.00 (d, 1 H, J 1,2 = 3.2 Hz, HA-1), 4.87 (dd, 1 H, J = 2.8 Hz, 2 J H-F = 52.0 Hz, HD-4), 4.73 (d, 1 H, J gem = 12.3 Hz, PhCHAO, ABq), 4.59 (d, 1 H, J 1,2 = 7.6 Hz, HD-1), 4.58 (d, 1 H, J 1,2 = 8.0 Hz, HC-1), 4.53 (d, 1 H, J gem = 12.4 Hz, PhCHBO, ABq), 4.46 (d, 1 H, J 1,2 = 7.8 Hz, HB-1), 4.34 (dd, 1 H, HA-2), 4.25 (d, 1 H, J = 2.8 Hz, HA-4), 4.16 (dd, 1 H, HA-5), 4.10 (dd, 1 H, HA-6b), 4.08 (dd, 1 H, HA-3), 4.02 (dd, 1 H), 3.92-3.80 (m, 6 H, HC-4), 3.81 (dd, 1 H, HD-3), 3.80-3.50 (m, 10 H, HD-2, HA-6a, HC-3, HD-2, HC-2), 2.31 (s, 3 H, Ac), 2.29 (s, 3 H, Ac); 13C NMR (D2O, 100.6 MHz): δ = 175.80 (C=O), 175.65 (C=O), 129.60, 129.40, 129.30, 105.90, 104.10, 102.85, 97.85, 79.80 (d, 1 J C-F = 178.5 Hz), 76.10 (d, 2 J C-F = 50.6 Hz), 73.90, 72.15 (d, 2 J C-F = 50.9 Hz), 71.50, 71.23, 70.25, 70.00, 62.25, 61.23, 56.20, 49.95, 23.50 (NAc), 23.20 (NAc). 19F NMR (CDCl3, 376.4 MHz): δ = -172.95 ppm. ESIMS (negative mode) Calcd for C35H53O20N2F (m/z) [M = 840]. Found: 839.6 [M]-. Compound 3: Rf = 0.5 (i-C3H9OH-HOAc-H2O, 3:1:1). 1 H NMR (D2O, DQF-COSY and ROESY, 400 MHz): δ = 7.50-7.20 (m, 5 H, ArH), 4.99 (d, 1 H, J 1,2 = 3.4 Hz, HA-1), 4.73 (d, 1 H, J gem = 12.6 Hz, PhCHAO, ABq), 4.61 (dq, 1 H, J = 2.8 Hz, J = 9.6 Hz, 2 J H-F = 68.0 Hz, HD-3), 4.58 (d, 1 H, J 1,2 = 7.6 Hz, HD-1), 4.55 (d, 1 H, J 1,2 = 8.6 Hz, HC-1), 4.52 (d, 1 H, J gem = 12.5 Hz, PhCHBO), 4.46 (d, 1 H, J 1,2 = 7.6 Hz, HB-1), 4.33 (dd, 1 H, HA-2), 4.24 (d, 1 H, J = 2.8 Hz, HA-4), 4.03 (d, 1 H, J = 3.2 Hz, HD-4), 4.16 (m, 1 H, HA-5), 4.07 (dd, 1 H, HA-6b), 4.04 (dd, 1 H, HA-3), 4.00 (dd, 1 H, HC-3), 3.91 (d, 1 H, J = 2.8 Hz, HB-4), 3.91-3.72 (m, 9 H), 3.64 (m, 2 H, HC-5, HB-3), 3.52 (dd, 1 H, HB-2), 2.31 (s, 3 H, Ac), 2.28 (s, 3 H, Ac); 13C NMR (D2O, 100.6 MHz): δ = 175.77 (C=O), 175.54 (C=O), 138.22, 130.07, 129.95, 129.71, 105.89, 103.41 (d, 3 J C-F = 12.7 Hz), 102.76, 97.58, 94.08 (d, 1 J C-F = 183.9 Hz), 79.81, 78.26, 76.15 (d, 2 J C-F = 17.8Hz), 75.32 (d, 3 J C-F = 6.8 Hz), 73.79, 73.75, 71.93, 71.05, 70.99, 70.86, 70.73, 70.13, 69.89, 68.15, 67.97, 62.29, 61.99, 61.97, 61.32, 56.43, 49.87, 23.57 (NAc), 23.26 (NAc). ESIMS (negative mode) Calcd for C35H53O20N2F (m/z) [M = 840]. Found: 839.5 [M]-, 875.5 [M + Cl]-