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Stereospecific α‐Sialylation by Site‐Selective Fluorination
Author(s) -
Hayashi Taiki,
Kehr Gerald,
Bergander Klaus,
Gilmour Ryan
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201812963
Subject(s) - chemistry , stereospecificity , glycomics , anomer , combinatorial chemistry , electrophile , fluorine , sialic acid , membrane , stereochemistry , glycan , biochemistry , organic chemistry , glycoprotein , catalysis
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−H δ+ →C−F δ− ), fluorine insertion simultaneously augments the anomeric effect, enhances electrophilicity at C2 and mitigates elimination. A stereochemical induction model is postulated that spans the S N continuum and validates the role of the C−F bond in orchestrating α‐selectivity.