The enantioselective synthesis of dideoxy-tetrafluorinated hexoses

Abstract

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, both in the pyranose and furanose form. 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 well as 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, and proceeds in good to excellent yields. NMR and X-ray crystallographic analysis of the tetrafluorinated methyl pyranoside derivatives confirms their 4C1 conformation.

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Identifiers

ORCID for Clement Q. Fontenelle: orcid.org/0000-0002-1630-3407

ORCID for Mark Light: orcid.org/0000-0002-0585-0843

ORCID for Bruno Linclau: orcid.org/0000-0001-8762-0170

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