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

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 (Ki = 8 vs 10 nM).

Graphical abstractThe nitrone 4 was synthesised from d-ribose. We described its transformations into fucosidase inhibitors, particularly the known 4-amino-l-lyxose 3 and the C-β-hydroxy-ethyl derivative 2c (Ki = 10 and 8 nM, respectively).Figure optionsDownload full-size imageDownload as PowerPoint slide