Enantioselective Synthesis of Dideoxy-tetrafluorinated Hexoses

Carbohydrates typically have low
affinities to protein binding
sites, and the development of carbohydrate mimetics with improved
binding is therefore of interest. Tetrafluorination of monosaccharides
is one of the strategies currently under investigation for that purpose.
The synthesis of the required tetrafluorinated monosaccharides is
achieved by a fluorinated building block approach. The enantioselective
synthesis of tetrafluorinated hexose derivatives is described here,
in both pyranose and furanose forms. In particular, the optimization
of the enantioselective synthesis of the previously reported 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexopyranose 3, 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexofuranose 4, and 2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose 5 is described as is the synthesis of two novel sugar derivatives,
3,4-dideoxy-3,3,4,4-tetrafluoro-d-threo-hexopyranose 6 and 3,4-dideoxy-3,3,4,4-tetrafluoro-d-erythro-hexopyranose 7. The key step of all syntheses is a
perfluoroalkyl lithium-mediated C–C bond formation, either
intramolecular or intermolecular, which proceeds in good to excellent
yields. NMR and X-ray crystallographic analyses of the tetrafluorinated
methyl pyranoside derivatives confirm their 4C1 conformation.