51515-96-9Relevant academic research and scientific papers
Convergent and stereoselective synthesis of iminosugar-containing Galf and UDP-Galf mimicks: Evaluation as inhibitors of UDP-Gal mutase
Liautard, Virginie,Desvergnes, Valerie,Itoh, Kenji,Liu, Hung-Wen,Martin, Olivier R.
, p. 3103 - 3115 (2008/09/19)
(Chemical Equation Presented) The synthesis of a UDP-Galf analog incorporating a 1,4-dideoxy-1,4-imino-D-galactitol skeleton α-linked to UMP by a 3C-tether and of a series of related pyrrolidine galactofuranose mimicks is reported. These compounds were obtained by way of the highly stereoselective reaction of silylated nucleophiles with a N-Cbz glucofuranosylamine which afforded the corresponding open-chain product with a 1,2-syn stereochemistry, as predicted from pionneering studies from Kobayashi. Cyclization of these intermediates afforded α-C-glycosides of imino-galactofuranose carrying various functional groups in the aglycone. Further elaboration of the α-C-allyl substituted derivative by cross-metathesis with a uridin-5′-yl vinylphosphonate provided, after deprotection, the desired original UDP-Galf mimicks. Cleavage of the benzyl ether protecting groups in the iminosugar component using BCl3 proved critical to the success of the synthetic plan. Several of the new 1,4-dideoxy-1,4-imino-D-galactitol derivatives were evaluated as inhibitors of UGM (UDP-galactopyranose mutase) from Escherichia coli; however, none of them exhibited less than mM activities toward this enzyme which catalyzes a crucial step of the biosynthesis of galactofuranose-containing bacterial cell-surface glycans.
