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Regioselective monodeprotection of peracetylated carbohydrates

Nature Protocols volume 7, pages 1783–1796 (2012)Cite this article

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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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Figure 1: General scheme of the regioselective monodeprotection of per-O-acetylated carbohydrates.
Figure 2
Figure 3: Per-O-acetylation of the different D-glycopyranosides.
Figure 4
Figure 5

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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

Authors and 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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  1. Marco Filice
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  2. Jose M Guisan
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  3. 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.

Corresponding author

Correspondence to Jose M Palomo.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Per-O-acetylation of carbohydrates (PDF 125 kb)

Supplementary Table 2

Regioselective enzymatic C-6 monodeprotection of per-O-acetylated glycopyranosides (PDF 173 kb)

Supplementary Table 3

Regioselective enzymatic monodeprotection of per-O-acetylated glycopyranosides (PDF 171 kb)

Supplementary Table 4

Synthesis of 4-hydroxy-tetraacetylated monosaccharides by acyl-chemical migration from the 6-OH monodeprotected tetraacetylated products (PDF 136 kb)

Supplementary Table 5

Synthesis of 3-hydroxy-tetraacetylated monosaccharides by acyl-chemical migration from the 6-OH monodeprotected tetraacetylated products (PDF 137 kb)

Supplementary Figure 1

HPLC trace for the regioselctive enzymatic hydrolysis of 1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (20) (PDF 551 kb)

Supplementary Figure 2

HPLC traces for the chemical acyl-migration of 39 to form 64 and 73 (PDF 528 kb)

Supplementary Figure 3

TLC of the chemo-enzymatic process starting from 1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (20) (PDF 427 kb)

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Filice, M., Guisan, J., Terreni, M. et al. Regioselective monodeprotection of peracetylated carbohydrates. Nat Protoc 7, 1783–1796 (2012). https://doi.org/10.1038/nprot.2012.098

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