Stereospecific α-Sialylation by Site-Selective Fluorination.

Abstract

Sialic acids are ubiquitous components of mammalian cell membranes and key regulators of cellular recognition events. Located at the non-reducing termini of bioactive gangliosides, these essential building blocks are fused to the polysaccharide core via a characteristic α-linkage, and rarely occur in the monomeric form. Effective chemical strategies to enable α-sialylation are urgently required to construct well-defined tools for glycomics. To complement existing chemoenzymatic strategies, an α-selective process has been devised based on the site-selective introduction of fluorine at C3 (more than 20 examples, up to 90 % yield). Predicated on localized particle charge inversion (C-Hδ+ →C-Fδ- ), fluorine insertion simultaneously augments the anomeric effect, enhances electrophilicity at C2 and mitigates elimination. A stereochemical induction model is postulated that spans the SN continuum and validates the role of the C-F bond in orchestrating α-selectivity.