Download PDF
Synlett 2003(9): 1364-1366
DOI: 10.1055/s-2003-40338
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Esterification of Various d-Glucopyranosides: Synthesis of a Fully Protected Disaccharide Unit of Hyaluronic Acid

Xin-An Lu, Chien-Hung Chou, Cheng-Chung Wang, Shang-Cheng Hung*
Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan
Fax: +886(2)27831237; e-Mail: schung@chem.sinica.edu.tw.;
Further Information

Publication History

Received 28 May 2003
Publication Date:
30 June 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

A highly regioselective esterification of various d-glucopyranosides with triethylamine and acid anhydrides in excellent yields is described here. Its application toward the synthesis of a fully protected disaccharide unit of hyaluronic acid is also highlighted.

Key words

carbohydrates - esterifications - hyaluronic acid

    References

  • 1 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  John Wiley and Sons, Inc.; New York: 1999. 
    Google Scholar
  • 2 Kim S. Chang H. Kim WJ. J. Org. Chem.  1985,  50:  1751 
    Google Scholar
  • 3 Grindley TB. Adv. Carbohydr. Chem. Biochem.  1998,  53:  17 
    Google Scholar
  • 4 Schelhaas M. Waldmann H. Angew. Chem., Int. Ed. Engl.  1996,  35:  2056 
    CrossrefGoogle Scholar
  • 6 Szeja W. Carbohydr. Res.  1983,  115:  240 
    Google Scholar
  • 7a Dasgupta F. Hay GW. Szarek WA. Shilling WL. Carbohydr. Res.  1983,  114:  153 
    CrossrefGoogle Scholar
  • 7b Eby R. Webster KT. Schuerch C. Carbohydr. Res.  1984,  129:  111 
    CrossrefGoogle Scholar
  • 7c Horton D. Priebe W. Varela O. Carbohydr. Res.  1985,  144:  317 
    CrossrefGoogle Scholar
  • 7d Hanessian S. Kagotani M. Carbohydr. Res.  1990,  202:  67 
    CrossrefGoogle Scholar
  • 8 Li Z.-J. Huang H.-Q. Cai M.-S. Carbohydr. Res.  1994,  265:  227 
    Google Scholar
  • 9 Zhang S.-Q. Li Z.-J. Wang A.-B. Cai M.-S. Feng R. Carbohydr. Res.  1998,  308:  281 
    Google Scholar
  • 10 Hung S.-C. Thopate SR. Wang C.-C. Carbohydr. Res.  2001,  330:  177 
    Google Scholar
  • 12 Schmidt RR. Kinzy W. Adv. Carbohydr. Chem. Biochem.  1994,  50:  21 
    PubMedGoogle Scholar
  • 13 The Chemistry, Biology and Medical Applications of Hyaluronan and its Derivatives   Laurent TC. Portland Press; London: 1998. 
    Google Scholar
  • 14 De Luca C. Lansing M. Martini I. Crescenzi F. Shen G.-J. O’Regan M. Wong C.-H. J. Am. Chem. Soc.  1995,  117:  5869 
    Google Scholar
  • 15a Slaghek TM. Nakahara Y. Ogawa T. Tetrahedron Lett.  1992,  33:  4971 
    Google Scholar
  • 15b Slaghek TM. Nakahara Y. Ogawa T. Kamerling JP. Vliegenthart JFG. Carbohydr. Res.  1994,  255:  61 
    Google Scholar
  • 15c Halkes KM. Slaghek TM. Hyppönen TK. Kruiskamp PH. Ogawa T. Kamerling JP. Vliegenthart JFG. Carbohydr. Res.  1998,  309:  161 
    Google Scholar
  • 15d Yeung BKS. Hill DC. Janicka M. Petillo PA. Org. Lett.  2000,  2:  1279 
    Google Scholar
  • 16a Slaghek TM. Hyppönen TK. Ogawa T. Kamerling JP. Vliegenthart JFG. Tetrahedron Lett.  1993,  34:  7939 
    Google Scholar
  • 16b Slaghek TM. Hyppönen TK. Ogawa T. Kamerling JP. Vliegenthart JFG. Tetrahedron: Asymmetry  1994,  5:  2291 
    Google Scholar
  • 16c Carter MB. Petillo PA. Anderson L. Lerner LE. Carbohydr. Res.  1994,  258:  299 
    Google Scholar
  • 16d Coutant C. Jacquinet J.-C. J. Chem. Soc., Perkin Trans. 1  1995,  1573 
    Google Scholar
  • 16e Blatter G. Jacquinet J.-C. Carbohydr. Res.  1996,  288:  109 
    Google Scholar
  • 17 Fischer B. Nudelman A. Ruse M. Herzig J. Gottlieb HE. Keinan E. J. Org. Chem.  1984,  49:  4988 
    Google Scholar
5

Following is the general procedure for the regioselective esterification of various d-glucopyranosyl diols. To a solution of the diol in CH2Cl2 (10 mL/g) was added acid anhydride (1.4 equiv) at r.t. under nitrogen. After stirring for 10 min, Et3N (9 equiv) was added to the mixture, and the whole solution was kept stirring overnight. MeOH (5 equiv) was added to quench the reaction, and the resulting solution was evaporated under reduced pressure. The syrup was dissolved in EtOAc, and the mixture was sequentially washed by water, aq sat. NaHCO3(twice), and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by either recrystallization in ethanol or flash column chromatography on silica gel to give the desired product.

11

Colorless crystals from chloroform/hexane, C20H19N3O6, fw = 397.14, crystal dimensions: 0.43 × 0.31 × 0.19 mm3, crystal system: orthorhombic, space group: P212121, unit-cell dimensions: a = 8.7073(7), b = 11.0684(21), c = 19.784(6) Å, V = 1906.7(7) Å3, Z = 4, ρcalcd = 1.384 gcm-3, wavelength = 0.7107 Å, F(000) = 831.85, mu = 0.10 mm-1, 2θ(max) = 50.0. The deposition number at the Cambridge Crystallographic Data Centre is CCDC 162431.

18

The selected physical data of key compounds is listed. Compound 22: [α]D 25 -103.1 (c 1.0, CHCl3). Mp 209-210 °C. IR (CHCl3): ν = 2956 (w), 2115 (s), 1751 (s), 1635 (m), 1374 (m), 1219 (s), 912 (w)cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.09 (d, J = 7.2 Hz, 2 H, ArH), 7.63 (t, J = 7.2 Hz, 1 H, ArH), 7.49 (t, J = 7.6 Hz, 2 H, ArH), 7.44-7.37 (m, 5 H, ArH), 5.81 (d, J = 8.3 Hz, 1 H, H-1), 5.53 (s, 1 H, benzylidene), 5.25-5.14 (m, 2 H, H-3′, H-4′), 5.05 (t, J = 8.3 Hz, 1 H, H-2′), 4.84 (d, J = 8.0 Hz, 1 H, H-1′), 4.35 (dd, J = 10.3, 4.8 Hz, 1 H, H-5), 3.84-3.73 (m, 5 H, H-2, H-3, H-4, H-6, H-5′), 3.64-3.60 (m, 1 H, H-6′), 3.61 (s, 3 H, OMe), 2.08 (s, 3 H, OAc), 2.01 (s, 3 H, OAc), 1.99 (s, 3 H, OAc). 13C NMR (100 MHz, CDCl3): δ = 170.08 (C), 169.34 (C), 169.30 (C), 166.77 (C), 164.37 (C), 136.76 (C), 134.09 (CH), 130.08 (CH), 129.17 (CH), 128.65 (CH), 128.31 (CH), 125.90 (CH), 101.54 (CH), 100.84 (CH), 93.68 (CH), 80.01 (CH), 79.39 (CH), 72.42 (CH), 72.08 (CH), 71.55 (CH), 69.25 (CH), 68.21 (CH2), 67.06 (CH), 65.02 (CH), 52.69 (CH3), 20.55 (CH3), 20.42 (CH3). HRMS (FAB, MH+) calcd for C33H36N3O15: 714.2146. Found: 714.2111. Anal. Calcd for C33H35N3O15: C, 55.54; H, 4.94; N, 5.89. Found: C, 55.41; H, 4.64; N, 5.55. Compound 23: [α]D 25 -66.2 (c 0.9, CHCl3). Mp 188-189 °C. IR (CHCl3): ν = 3417 (w), 2955 (m), 1756 (s), 1751 (s), 1735 (s), 1654 (m), 1249 (s), 1084 (s), 753 (m)cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 7.5 Hz, 2 H, ArH), 7.60 (t, J = 7.5 Hz 1 H, ArH), 7.48-7.44 (m, 4 H, ArH), 7.41-7.37 (m, 3 H, ArH), 6.29 (d, J = 7.9 Hz, 1 H, H-1), 5.87 (d, J = 7.9 Hz, 1 H, NH), 5.52 (s, 1 H, benzylidene), 5.23-5.15 (m, 2 H, H-3′, H-4′), 5.00 (t, J = 7.7 Hz, 1 H, H-2′), 4.90 (d, J = 7.7 Hz, 1 H, H-1′), 4.45 (t, J = 8.7 Hz, 1 H, H-3), 4.36 (dd, J = 8.9, 3.3 Hz, 1 H, H-6), 3.95-3.89 (m, 2 H, H-2, H-4), 3.82-3.72 (m, 3 H, H-5, H-5′, H-6), 3.62 (s, 3 H, OMe), 1.99 (s, 3 H, OAc), 1.98 (s, 3 H, OAc), 1.96 (s, 3 H, OAc), 1.94 (s, 3 H, OAc). 13C NMR (100 MHz, CDCl3): δ = 170.42 (C), 170.05 (C), 169.43 (C), 169.39 (C), 167.08 (C), 164.81 (C), 136.97 (C), 133.82 (CH), 130.09 (CH), 129.12 (CH), 128.65 (CH), 128.60 (CH), 128.29 (CH), 126.07 (CH), 101.51 (CH), 99.67 (CH), 92.38 (CH), 79.76 (CH), 77.32 (CH), 72.09 (CH), 71.56 (CH), 69.24 (CH), 68.57 (CH2), 66.63 (CH), 55.43 (CH), 52.68 (CH3), 23.29 (CH3), 20.53 (CH3), 20.43 (CH3). HRMS (FAB, MH+) calcd for C35H40NO16: 730.2347. Found: 730.2360. Anal. Calcd for C35H39NO16: C, 57.61; H, 5.39; N, 1.92. Found: C, 57.58; H, 5.33; N, 1.85.