890028-53-2Relevant academic research and scientific papers
A new methodology for the synthesis of fluorinated exo-glycals and their time-dependent inhibition of UDP-galactopyranose mutase
Caravano, Audrey,Dohi, Hirofumi,Sinay, Pierre,Vincent, Stephane P.
, p. 3114 - 3123 (2006)
Fluorinated carbohydrates constitute a very important class of mechanistic probes for glycosyl-processing enzymes. In this study, we describe the first synthesis of fluorinated and phosphonylated exo-glycals and their corresponding nucleotide sugars in the galactofuranose series. The synthetic protocol that we have developed is a Selectfluor-mediated fluorination/ elimination sequence on phosphonylated exo-glycals, and it offers a new entry into fluorinated carbohydrate chemistry. The challenging E/Z stereochemical assignment of the resulting tetra substituted alkenes, which bear an alkoxy, an alkyl, a fluoro, and a phosphonyl group, has been achieved through NMR experiments. The corresponding (E)- and (Z)-nucleotide fluorosugars have been prepared and tested as inhibitors of UDP-galactopyranose mutase (UGM). UGM is a flavoenzyme that catalyzes the isomerization of uridine diphosphate(UDP)-gal actopyranose into UDP-galactofuranose, a key step of the biosynthesis of important mycobacterial cell-wall glycoconjugates. The two diastereomeric molecules were found to display timedependent inactivation of UGM, as expected from preliminary results using non-fluorinated exo-glycal nucleotides. The inhibitory properties of the two fluorinated molecules led us to suggest that the inactivation mechanism proceeds through two-electron processes, despite the presence of the flavin cofactor within the UGM catalytic site.
