Oligosaccharides carry out critical functions in a vast array of biochemical processes, including, but not limited to, the immune response, cell adhesion, and protein folding. However, our understanding of the molecular basis of carbohydrate function remains constrained by the challenges associated with synthesizing stereochemically pure glycosides for study. Here we demonstrate that highly β-selective glycosylation reactions can be achieved when the electronics of a sulfonyl chloride activator and the reactivity of a glycosyl donor hemiacetal are matched. Specificlly, there is an inverse relationship between the intrinsic reactivity of the donor (as measured by Relative Reactivity Values) and the electronics of the optimal arylsulfonate for each glycosylation (Hammett Sigma Constant). While these reactions are compatible with the acid- and base-sensitive protecting groups that are commonly used in oligosaccharide synthesis, these protecting groups are not relied upon to control selectivity. Instead, β-selectivity arises from the stereoinversion of an α-glycosyl arylsulfonate in an SN2-like mechanism. Our mechanistic proposal is supported by NMR studies, kinetic isotope effect (KIE) measurements, and DFT calculations.

Matching glycosyl donor reactivity to sulfonate leaving group ability permits SN2 glycosylations

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.