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Synlett 2003(7): 0979-0982
DOI: 10.1055/s-2003-39312
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Polymer - Resin Hybrid Capture - Release Strategy for Rapid Oligo­saccharide Construction

Shinya Hanashimaa,b, Shino Manabea,c, Yukishige Ito*a
a RIKEN (The Institute of Physical and Chemical Research), Hirosawa, Wako-shi, Saitama, 351-0198, Japan
Fax: +81(48)4624680; e-Mail: yukito@postman.riken.go.jp;
b Department of Applied Biological Science, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, 278-8510, Japan
c PRESTO, JST, Kawaguchi, Saitama, 332-0012, Japan
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Publication History

Received 25 March 2003
Publication Date:
20 May 2003 (online)

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Abstract

The polymer-resin hybrid type capture-release purification strategy for oligosaccharide synthesis was renewed as more rapid and straightforward manner. The substrate for N-acetylglucosaminyltransferase V trisaccharide was synthesized rapidly on PEG (poly (ethylene glycol) methyl ether) and purified by use of the strategy.

Key words

capture-release purification strategy - carbohydrates - glycosylations - oligosaccharides - polymer-supported synthesis

    References

  • 1a Ito Y. Manabe S. Curr. Opin. Chem. Biol.  1998,  2:  701 
    CrossrefPubMedSearch in Google Scholar
  • 1b Seeberger PH. Haase W.-C. Chem. Rev.  2000,  100:  4349 
    CrossrefPubMedSearch in Google Scholar
  • 1c Sears P. Wong C.-H. Science  2001,  291:  2344 
    CrossrefPubMedSearch in Google Scholar
  • 2a Ando H. Manabe S. Nakahara Y. Ito Y. J. Am. Chem, Soc.  2001,  123:  3848 
    CrossrefSearch in Google Scholar
  • 2b Ando H. Manabe S. Nakahara Y. Ito Y. Angew. Chem. Int. Ed.  2001,  40:  4725 
    CrossrefSearch in Google Scholar
  • 2c Ito Y. Manabe S. Chem.-Eur. J.  2002,  8:  3076 
    CrossrefSearch in Google Scholar
  • 3a Kanie O. Crawley SC. Palcic MM. Hindsgaul O. Carbohydr. Res.  1993,  243:  139 
    Search in Google Scholar
  • 3b Lu PP. Hindsgaul O. Compston CA. Palcic MM. Bioorg. Med. Chem.  1996,  4:  2011 
    Search in Google Scholar
  • 4a Granovsky M. Fata J. Pawling J. Muller WJ. Khokha R. Dennis JW. Nature Medicine  2000,  6:  306 
    CrossrefSearch in Google Scholar
  • 4b Sasai K. Ikeda Y. Fujii T. Tsuda T. Taniguchi N. Glycobiology  2002,  12:  119 
    CrossrefSearch in Google Scholar
  • 5a Hodosi G. Kováè P. J. Am. Chem. Soc.  1997,  119:  2335 
    CrossrefSearch in Google Scholar
  • 5b Hodosi G. Kováè P. Carbohydr. Res.  1998,  308:  63 
    CrossrefSearch in Google Scholar
  • 6a

    Separation of β-mannoside and 3-O-alkylated regioisomer was difficult at this stage. For easier separation, the remained hydroxy groups were acetylated and the anomeric acetyl group of the regio isomer was removed by piperidine. The linkage of stereochemistry of anomeric position of 6 was confirmed by 1H NMR analysis (JCH = 156.6 Hz in C6D6) and NOE experiment between H-1 and H-5.
  • 6b Bock K. Pedersen C. J. Chem. Soc., Perkin Trans. 2  1974,  293 
  • 9 Inanaga J. Hirai K. Saeki H. Katsuki T. Yamaguchi M. Bull. Chem. Soc. Jpn.  1979,  52:  1989 
    CrossrefSearch in Google Scholar
  • 10 Boons G.-J. Bowers S. Coe DM. Tetrahedron Lett.  1997,  38:  3773 
    Search in Google Scholar
  • 12 Van Boeckel CAA. Beetz T. Tetrahedron Lett.  1983,  24:  3775 
    Search in Google Scholar
  • 17a

    1H NMR (500 MHz, D2O): δ = 4.71 (br s, 1 H, H-1′), 4.60 (s, 1 H, H-1), 4.37 (d, 1 H, J = 8.7 Hz, H-1′′), 3.78 (m, 1 H, H-2′), 3.78-3.74 (m, 2 H, H-2, H-6a), 3.72-3.69 (m, 2 H, H-6a′, H-6a′′), 3.67-3.62 (m, 2 H, H-3′, CH2O), 3.58-3.50 (m, 2 H, H-6b, H-6b′′), 3.48-3.39 (m 9 H, H-2′′, H-3, H-4, H-5′, H-6b′, OMe, OCH2), 3.35 (dd, J = 8.3, 10.6 Hz, 1 H, H-3′′), 3.32-3.20 (m, 4 H, H-4′, H-4′′, H-5, H-5′′), 2.18 (dd, J = 7.4, 7.4 Hz, 2 H), 1.85 (s, 3 H), 1.40-1.39 (m, 4 H), 1.10 (m, 8 H). 13C NMR (125 MHz, D2O): δ = 178.1, 175.0, 100.1, 99.7, 96.9, 76.4, 76.0, 74.6, 73.5, 73.4, 73.0, 70.7, 70.3, 70.1, 69.8, 67.5, 66.8, 66.2, 61.8, 60.8, 55.5, 52.2, 33.9, 28.8-28.2, 25.2, 24.5, 22.5. [α]D 25 -18.4 (c 0.32, H2O).
  • 17b Tahir SH. Hindsgaul O. Can. J. Chem.  1986,  64:  1771 
    Search in Google Scholar
7

During the benzylation, the methyl group was changed to benzyl ether (7.9%) and carboxylic acid (9.5%). As the separation of methyl ester and benzyl ester was difficult, the mixture of the ester was hydrolyzed.

8

Previously, the average molecular weight 550 PEG was used as a polymer support and it works as ‘tag’ efficiently. However, in this case, its molecular weight is not sufficient for the ‘tag’ for the purification because of lack of enough polarity.

11

Although the characteristic ‘mountain’ like shape of the spectra of monosaccharide and disaccharide were not completely separated, the monitoring of progress of the reaction was possible. After the reaction, quite high purity of PEG-bound disaccharide was confirmed by 1H NMR spectroscopy.

13

The ratio of α:β at the newly formed anomeric carbon is 1:9.9.

14

Compound 14 was prepared from Boc-β-Ala-Merrifield resin (0.66 mmol/g) in 2 steps. i) TFA, CH2Cl2, then Et3N; ii) Boc-S-tert-butylmercapto-l-cysteine, HOBt, N, N′-diisopropylcarbodiimide, DMF. After peptide bond formation, ninhydrin test showed >99% yield.

15

After releasing step, further purification of the released product was not necessary in the case of Boc group protected cysteine, compared to the Fmoc version.

16

The acetyl group of glucosamine was deprotected under esterification by use of(trimethylsilyl)diazomethane.