1. Synthesis of 4-amino-4,5-dideoxy-l-lyxofuranose derivatives and their evaluation as fucosidase inhibitors
- Author
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Albert Defoin, Céline Tarnus, Carine Chevrier, and Didier Le Nouen
- Subjects
Pyrrolidines ,Stereochemistry ,Ribose ,Pentoses ,Drug Evaluation, Preclinical ,Alcohol ,Kidney ,Biochemistry ,Analytical Chemistry ,Nitrone ,Structure-Activity Relationship ,chemistry.chemical_compound ,Hydrolysis ,Animals ,Structure–activity relationship ,Fucosidase ,Enzyme Inhibitors ,Furans ,alpha-L-Fucosidase ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Amino Sugars ,General Medicine ,Enol ,Cycloaddition ,Models, Chemical ,chemistry ,biology.protein ,Cattle - Abstract
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 α-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 10nM).
- Published
- 2011
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