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Synlett 2004(14): 2594-2596  
DOI: 10.1055/s-2004-834811
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 6-Branched Cyclo-(1→3)-glucohexaose and Glucooctaose

Zicheng Wu, Fanzuo Kong*
Research Center for Eco-Environmental Sciences, Academia Sinica, P. O. Box 2871, Beijing 100085, P. R. China
Fax: +86(10)62923563; e-Mail: fzkong@mail.rcees.ac.cn;
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Publication History

Received 3 August 2004
Publication Date:
20 October 2004 (online)

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Abstract

The cyclization precursors nonasaccharide 3 and dodecasaccharide 8 were obtained, respectively, from the corresponding 4-methoxyphenyl glycosides 1 and 6 via oxidative cleavage of 1-OMp followed by selective 1-O-trichloroacetimidate formation. TMSOTf-promoted cycloglycosylation of 3 and 8 went smoothly giving α-linked cyclized nonasaccharide 4 and dodecasaccharide 9. Finally, deacylation of 4 and 9 furnished the target cycloglucans 5 and 10 consisting of alternate β- and α-(1→3)-linked cycloglucohexaose backbone bearing three β-(1→6)-linked glucose side chains and cycloglucooctaose backbone bearing four β-(1→6)-linked glucose side chains, respectively. The side chains were ­attached at the glucose residue of the backbone with α-linkage.

Key words

cyclodextrin - cyclo-glycosylation - glucans

    References

  • 1a Kuyama H. Nukada T. Ito Y. Nakahara Y. Ogawa T. Carbohydr. Res.  1995,  268:  C1 
    CrossrefGoogle Scholar
  • 1b Takahashi Y. Ogawa T. Carbohydr. Res.  1987,  164:  277 
    CrossrefGoogle Scholar
  • 2 Irie T. Uekama K. J. Pharm. Sci.  1997,  86:  147 
    CrossrefGoogle Scholar
  • 3 Kobayashi S. Kainuma K. Franch D. In Proc. 1st Int. Symp. on Cyclodextrins (Budapest, 1981)   Szejtli J. D. Reidel; Dordrecht: 1982.  p.51 
    Google Scholar
  • 4 Kobayashi S. Maruyam K. Kainuma K. J. Jpn. Soc. Starch Sci.  1983,  30:  231 
    Google Scholar
  • 5 Koizumi K. Okada Y. Kubota Y. Utamura T. Chem. Pharm. Bull.  1987,  35:  3413 
    Google Scholar
  • 6 Okada Y. Kuboda Y. Koizumi K. Hizukuri S. Ohfuji T. Ogata K. Chem. Pharm. Bull.  1986,  36:  2176 
    Google Scholar
  • 7 Yamamoto Y. Kubota Y. Inoue Y. Chûjo R. Kobayashi S. Chem. Lett.  1988,  495 
    Google Scholar
  • 8 Ning J. Zhang W. Yi Y. Yang G. Wu Z. Yi J. Kong F. Bioorg. Med. Chem.  2003,  11:  2193 
    CrossrefGoogle Scholar
  • 9 Yan J. Zong H. Shen A. Chen S. Yin X. Shen X. Liu W. Gu X. Gu J. Int. Immunopharmacol.  2003,  3:  1861 
    Google Scholar
  • 10 Wu Z. Ning J. Kong F. Carbohydr. Res.  2003,  338:  2203 
    CrossrefGoogle Scholar
  • 12a Zeng Y. Ning J. Kong F. Tetrahedron Lett.  2002,  43:  3729 
    CrossrefGoogle Scholar
  • 12b Zeng Y. Ning J. Kong F. Carbohydr. Res.  2003,  338:  307 
    CrossrefGoogle Scholar
11

Cyclization Procedure: Compound 3 (400 mg, 0.115 mmol) or 8 (400 mg, 0.087 mmol) was dried under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (15 mL). TMSOTf (5 µL) was added dropwise at -20 °C under N2 protection. The reaction mixture was stirred for 3 h, during which time the temperature was gradually raised to ambient temperature. Then the mixture was neutralized with Et3N. Concentration of the reaction mixture, followed by purification on a silica gel column with 2:1 petroleum ether-EtOAc as the eluent gave 4 (154 mg, 40.1%) or 9 (125 mg, 32.4%).

13

All the new compounds involved in the study were identified by 1H NMR and/or 13C NMR spectrometry, and elemental analyses. Selected data for some important compounds:
Compound 3: [α]D +46.3 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 8.41 (s, 1 H, C=NH), 6.31 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.97 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.92 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.88 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.85 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.79 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.61 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.56 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.50 (d, 1 H, J 1,2 = 7.9 Hz, H-1). 13C NMR (100 MHz, CDCl3): δ = 101.5, 101.4, 100.7, 100.3, 100.0, 99.8 (6 β-C-1), 94.2, 93.9, 92.8 (3 α-C-1). Anal. Calcd for C170H170Cl3NO73: C, 58.46; H, 4.87. Found: C, 58.72; H, 4.99.
Compound 4: [α]D +48.6 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 5.01 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.93 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.90 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.80 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.77 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.70 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.55 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.50 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.46 (d, 1 H, J 1,2 = 7.9 Hz, H-1). 13C NMR (100 MHz, CDCl3): δ = 102.0, 101.5, 101.4, 100.4, 100.4, 100.2 (6 β-C-1), 94.0, 92.1, 89.9 (3 α-C-1). MALDI-TOF MS: Calcd for C168H168O72: 3339.1 [M]. Found: 3363 [M + Na].

Compound 5: [a]D +16.7 (c 1.0, H2O). 1H NMR (400 MHz, CDCl3): d = 5.39 (d, 3 H, J = 3.8 Hz, 3 H-1), 4.55 (d, 6 H, J = 7.9 Hz, 6 H-1), 4.30-4.20 (m, 4 H), 4.02-3.97 (m, 12 H), 3.86-3.70 (m, 20 H), 3.59-3.50 (m, 11 H), 3.45-3.33 (m, 7 H). 13C NMR (100 MHz, D2O): d = 102.8 (6 C-1 for b bonds, J C-H = 163.3 Hz), 99.1 (3 C-1 for a bond, J C-H = 171.6 Hz), 85.1, 84.4, 76.4, 76.0, 75.9, 75.6, 73.4, 73.2, 73.1, 72.2, 71.5, 71.2, 71.0, 70.8, 70.3, 69.9, 69.6, 69.0, 68.8, 68.4, 67.7 (C-2,3,4,5,6, some signals were overlapped). MALDI-TOF MS: Calcd for C54H90O45: 1459.3 [M]. Found: 1482.6 [M + Na].
Compound 8: [a]D +37.5 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): d = 8.40 (s, 1 H, C=NH), 6.30 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.96 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.93 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.90 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.85 (d, 2 H, J 1,2 = 3.6 Hz, 2 H-1), 4.80 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.65 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.62 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.54 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.44 (d, 1 H, J 1,2 = 7.9 Hz, H-1). 13C NMR (100 MHz, CDCl3): d = 101.8, 101.6, 101.5, 100.9, 100.5, 100.3, 100.1, 99.8 (8 b-C-1), 94.5, 94.1, 93.6, 92.7 (4 a-C-1). Anal. Calcd for C226H226Cl3NO97: C, 58.82; H, 4.90. Found: C, 60.07; H, 4.94.
Compound 9: [a]D +42.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): d = 4.98 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.96 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.90 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.86 (d, 2 H, J 1,2 = 3.6 Hz, 2 H-1), 4.81 (d, 1 H, J 1,2 = 3.6 Hz, H-1), 4.76 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.66 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.62 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.53 (d, 1 H, J 1,2 = 7.9 Hz, H-1), 4.45 (d, 1 H, J 1,2 = 7.9 Hz, H-1). 13C NMR (100 MHz, CDCl3): d = 102.3, 101.7, 101.5, 101.5, 100.8, 100.5, 100.3, 99.9 (8 b-C-1), 94.7, 94.3, 93.7, 90.0 (4 a-C-1). MALDI-TOF MS: Calcd for C224H224O96: 4452 [M]. Found: 4475 [M + Na].
Compound 10: [a]D +24.1 (c 1.0, H2O). 1H NMR (400 MHz, CDCl3): d = 5.24 (d, 4 H, J = 3.6 Hz, 4 H-1), 4.40 (d, 8 H, J = 8.0 Hz, 8 H-1), 4.13-4.05 (m, 12 H), 3.92-3.80 (m, 22 H), 3.70-3.54 (m, 26 H), 3.42-3.32 (m, 12 H). 13C NMR (100 MHz, D2O): d = 102.8 (8 C-1 for b bonds, J C-H = 164.3 Hz), 99.1 (4 C-1 for a bond, J C-H = 173.1 Hz), 82.6, 81.9, 75.9, 75.6, 73.5, 73.2, 73.0, 72.8, 72.5, 72.4, 72.2, 71.8, 71.2, 70.8, 69.9, 69.6, 68.4, 67.7, 60.8, 60.5 (C-2,3,4,5,6, some signals were overlapped). MALDI-TOF MS: Calcd for C72H120O60: 1945.7 [M]. Found: 1969.0 [M + Na].