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Synthesis and X-ray Structure of (2R, 3R, 4R, 5R)-3,4,5-Tris-Benzyloxy-2-Benzyloxymethyl-Piperidin-1-ol, the N-Hydroxy-Analogue of 2,3,4,6-Tetra-O-Benzyl-1-Deoxymannojirimycin

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Abstract

The title compound 8 was obtained for the first time by hydride-mediated reduction of the d-fructose-derived nitrone 9. The N-hydroxy piperidine 8 is a precursor of the N-hydroxy analogue of DMJ, a potent inhibitor of α-mannosidases. It was isolated as colorless crystals (triclinic, P1 space group) exhibiting the following cell parameters: a = 9.947(2) Å; b = 12.155(2) Å; c = 13.864(5) Å; α = 100.98(3)°; β = 97.94(2)°; γ = 109.50(1)°. The X-ray analysis of a monocrystal of 8 allowed confirmation of its relative configurations and showed the anti orientation of its N-hydroxy group. This structural feature should be useful for considering the interaction of N-hydroxy iminosugars with the recognition site of carbohydrate processing enzymes.

Index Abstract

The title compound 8 was prepared for the first time by hydride-mediated reduction of the d-fructose-derived nitrone 9. Compound 8 is a precursor of the N-hydroxy analogue of DMJ, a potent inhibitor of α-mannosidases. The X-ray analysis allowed confirmation of the relative configurations of 8 and showed the anti orientation of its N-hydroxy group. This structural feature will be useful for considering the interaction of N-hydroxy-iminosugars with specific biological targets.

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Acknowledgments

We thank Mrs Marie-Louise Dheu-Andries for her helpful support. E. R. is grateful to the French Ministry of Education, Research and Technology (MENRT) for a doctoral fellowship. This work was supported by the CNRS, the Université Joseph Fourier and the Agence Nationale pour la Recherche (Grant No. ANR-05-JCJC-0130-01).

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Authors and Affiliations

  1. Département de Chimie Moléculaire (SERCO) UMR-5250, ICMG FR-2607, CNRS, Université Joseph Fourier, BP 53, 38041, Grenoble Cedex 09, France

    Emilie Racine, Christian Philouze & Sandrine Py

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  1. Emilie Racine
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  2. Christian Philouze
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  3. Sandrine Py
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Correspondence to Sandrine Py.

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Racine, E., Philouze, C. & Py, S. Synthesis and X-ray Structure of (2R, 3R, 4R, 5R)-3,4,5-Tris-Benzyloxy-2-Benzyloxymethyl-Piperidin-1-ol, the N-Hydroxy-Analogue of 2,3,4,6-Tetra-O-Benzyl-1-Deoxymannojirimycin. J Chem Crystallogr 39, 494–499 (2009). https://doi.org/10.1007/s10870-008-9506-8

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