PREPARATION OF FLUORINATED GALACTOSYL NUCLEOSIDE DIPHOSPHATES TO STUDY THE MECHANISM OF THE ENZYME GALACTOPYRANOSE MUTASE

A novel latent-->active phosphorylation strategy has been employed for the preparation of two fluorinated nucleoside diphosphates (compounds I and II). The strategy is based on the isomerisation of substituted allyl to vinyl glycosides which were subsequently phosphorylated by tr eatment with dibenzyl hydrogen phosphate, N-iodosuccinimide and a cata lytic amount of trimethylsilyl triflate. This methodology is very suit able for the preparation of nucleoside diphosphates that have a modifi cation in the saccharide moiety since the allyl moiety serves first as an anomeric protecting group, allowing for protecting-group manipulat ion and functionalisation of the sugar ring, but after isomerisation t o the corresponding vinyl glycoside it acts as an anomeric leaving gro up. The 2-F and 4-F Gal-UDP derivatives I and II do not inhibit the en zyme galactopyranose mutase in the direction pyranose --> furanose but both compounds have been found to inhibit the reverse reaction.