title: Synthesis of 4-amino-4,5-dideoxy-L-lyxofuranose derivatives and their evaluation as fucosidase inhibitors.
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).
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, FRE 3253, École Nationale Supérieure de Chimie de Mulhouse, Université de Haute-Alsace, 3, rue Alfred Werner, F-68093 Mulhouse Cédex, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Chevrier
authors.forename: Didier
authors.initials: D
authors.lastname: Le Nouën
authors.forename: Albert
authors.initials: A
authors.lastname: Defoin
authors.forename: Céline
authors.initials: C
authors.lastname: Tarnus
mesh_terms: D000606:Amino Sugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000737:chemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008956:Models, Chemical; D010429:Pentoses / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D012266:Ribose / Q000737:chemistry; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors*
chemical_list: D000606:Amino Sugars; D004791:Enzyme Inhibitors; D005663:Furans; D010429:Pentoses; D011759:Pyrrolidines; C043333:lyxose; D012266:Ribose; D005644:alpha-L-Fucosidase