The function of carbohydrates in biological systems has been the topic of intensive study. Most recently, glycoprotein recognition has been reported to be essential in cellular trafficking', viral infectivity', cancer metastasis3, and immunological regulation4. Given these important roles and the potential for novel therapeutic intervention' in a number of disease states, the modulation of glycoprotein synthesis/degradation or the antagonism of lectin binding sites has become an expanding area of research.
Fluorinated carbohydrates are valuable tools for the study of mammalian cell metabolism, transport, enzyme specificity and mechanism, as well as potential therapeutic agents in their own right6. Substitution of carbohydrate hydroxyl groups with fluorine atoms provides analogues which are sterically similar and polarized. Fluorine substitution also stabilizes glycosidic linkages to cleavage by electronically destabilizing the developing positive charge in oxonium intermediates during glycoside hydrolysis7.
Our studies involving glycosidase inhibitors8 required the synthesis of suitably protected 4deoxy-4-fluoro-D-galactopyranose derivatives as glycosyl donors. A survey of the literature revealed two procedures for the preparation of these analogues; however, each of them involved elaborate protection-deprotection protocols'. Furthermore, no synthesis of a preferred glycosyl donor, 2,3,6-tri-Oacetyl-4-deoxy-4-fluoro-a-D-galactopyranosyl bromide had been published.
A number of workers have reported successful regioselective acylations and alkylations of polyols involving stannylation methodology'". In one paper", stannylation of methyl a-o-glucopyranoside, followed by benzoylation with excess benzoyl chloride, afforded methyl 2,6-di-0-benzoylti-o-glucopyranoside as the major product, with the tribenzoylated adduct as a contaminant. We believed that the use of a sterically unencumbered acylating agent such as acetyl chloride would