4.5 Article

Synthesis of 4-amino-4,5-dideoxy-L-lyxofuranose derivatives and their evaluation as fucosidase inhibitors

Journal

CARBOHYDRATE RESEARCH
Volume 346, Issue 10, Pages 1202-1211

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carres.2011.03.030

Keywords

Aminolyxose; Aminosugars; Fucosidase inhibition

Funding

  1. Ministere de l'Enseignement et de la Recherche
  2. Universite de Haute-Alsace
  3. Ecole Nationale de Chimie de Mulhouse

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The nitrone 4 (4,5-dideoxy-4-hydroxylamino-3,4-O-isopropylidene-L-lyxofuranose) was synthesised from D-ribose and used as key intermediate for the preparation of fucosidase inhibitors. We describe two transformations of 4. Hydrolysis with aqueous sulfur dioxide gave the known potent nanomolar inhibitor 4-amino-4,5-dideoxy-L-lyxofuranose (3). 1,3-Dipolar cycloaddition with enol ethers led to the related 1,2,5,6-tetradeoxy-2,5-imino-L-altroheptonic ester 2a, acid 2b and the corresponding heptitol 2c. The new iminosugars have been evaluated for their inhibitory activity against alpha-L-fucosidase from bovine kidney. The alcohol 2c turned out to be a potent inhibitor in the same range as the amino-sugar 3 (K-i = 8 vs 10 nM). (C) 2011 Elsevier Ltd. All rights reserved.

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