Résumé

The Garcia-Gonzalez reaction Of D-glucose and ethyl acetoacetate generated ethyl 5-[(1'S)-D-erythrosyl]-2-methyl-3-furoate (5), which was converted to ethyl 5-[(1'R)-1',4'-dideoxy-1',4'-imino-D-erythrosyl]-2-methyl-3-furoate (3c) and to ethyl 5-[(1'S)-1',4'-dideoxy-1',4'-imino-D-erythrosyl]-2-methyl-3-furoate (4c). Similar methods were developed to generate other carboxylic acid derivatives such as methyl (see 3e and 4e), isopropyl (see 3f), and butyl esters (see 3g), S-phenyl (see 3a) and S-ethyl thioesters (see 3m), N-benzylcarboxamides 3b and 4b, glycine-derived amide 3h, and N-phenyl (see 3i), N-isopropyl (see 3j and 4j), N,N-diethyl- (see R and 4k), and N-ethyl-carboxamides (see 31). All the new 5-(1',4'-dideoxy-1',4'-imino-D-erythrosyl)-3-furoic acid (=5-[(3S,4R)-3,4-dihydroxypyrrolidin-2-yl)furan-3-carboxylic acid) derivatives 3 and 4 were assayed for inhibitory activity towards 25 commercially available glycosidases. Derivative 3a with a S-phenyl thioester group is a good and selective alpha-L-fucosidase inhibitor (K-i 2 - 4 mum), whereas 4b (with a N-benzylcarboxamide group) is a good beta-galactosidase inhibitor.

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