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Regioselective monodeprotection of peracetylated carbohydrates

Nature Protocols volume 7, pages 17831796 (2012) | Download Citation

Abstract

This protocol describes the regioselective deprotection of single hydroxyls in peracetylated monosaccharides and disaccharides by enzymatic or chemoenzymatic strategies. The introduction of a one-pot enzymatic step by using immobilized biocatalysts obviates the requirement to carry out tedious workups and time-consuming purifications. By using this straightforward protocol, different per-O-acetylated glycopyranosides (mono- or disaccharides, 1-substituted or glycals) can be transformed into a whole set of differentially monodeprotected 1-alcohols, 3-alcohols, 4-alcohols and 6-alcohols in high yields. These tailor-made glycosyl acceptors can then be used for stereoselective glycosylation for oligosaccharide and glycoderivative synthesis. They have been successfully used as building blocks to synthesize tailor-made di- and trisaccharides involved in the structure of lacto-N-neo-tetraose and precursors of the tumor-associated carbohydrate antigen T and the antitumoral drug peracetylated β-naphtyl-lactosamine. We are able to prepare a purified monoprotected carbohydrate in between 1 and 4 d. With this protocol, the small library of monodeprotected products can be synthesized in 1–2 weeks.

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Acknowledgements

This work was supported by The Spanish National Research Council (CSIC) and the Spanish Ministry of Science. We acknowledge Á. Berenguer (Instituto Universitario de Materiales, Universidad de Alicante) for his help during the writing of this paper.

Author information

Affiliations

  1. Departamento de Biocatálisis, Instituto de Catálisis (CSIC), Madrid, Spain.

    • Marco Filice
    • , Jose M Guisan
    •  & Jose M Palomo
  2. Dipartimento di Scienze del Farmaco, Università di Pavia, Pavia, Italy.

    • Marco Terreni

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Contributions

M.F. and J.M.P. performed the experiments; M.F. and J.M.P. analyzed data; J.M.P. and M.F. wrote the manuscript; J.M.P. and J.M.G. designed the study and experiments; and M.F. and M.T. designed the study for glycoderivative synthesis.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jose M Palomo.

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    Per-O-acetylation of carbohydrates

  2. 2.

    Supplementary Table 2

    Regioselective enzymatic C-6 monodeprotection of per-O-acetylated glycopyranosides

  3. 3.

    Supplementary Table 3

    Regioselective enzymatic monodeprotection of per-O-acetylated glycopyranosides

  4. 4.

    Supplementary Table 4

    Synthesis of 4-hydroxy-tetraacetylated monosaccharides by acyl-chemical migration from the 6-OH monodeprotected tetraacetylated products

  5. 5.

    Supplementary Table 5

    Synthesis of 3-hydroxy-tetraacetylated monosaccharides by acyl-chemical migration from the 6-OH monodeprotected tetraacetylated products

  6. 6.

    Supplementary Figure 1

    HPLC trace for the regioselctive enzymatic hydrolysis of 1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (20)

  7. 7.

    Supplementary Figure 2

    HPLC traces for the chemical acyl-migration of 39 to form 64 and 73

  8. 8.

    Supplementary Figure 3

    TLC of the chemo-enzymatic process starting from 1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (20)

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DOI

https://doi.org/10.1038/nprot.2012.098

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