Issue 3, 2017

The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

Abstract

A set of model nucleophiles of gradually changing nucleophilicity is used to probe the glycosylation reaction mechanism. Glycosylations of ethanol-based acceptors, bearing varying amounts of fluorine atoms, report on the dependency of the stereochemistry in condensation reactions on the nucleophilicity of the acceptor. Three different glycosylation systems were scrutinized, that differ in the reaction mechanism, that – putatively – prevails during the coupling reaction. It is revealed that the stereoselectivity in glycosylations of benzylidene protected glucose donors are very susceptible to acceptor nucleophilicity whereas condensations of benzylidene mannose and mannuronic acid donors represent more robust glycosylation systems in terms of diastereoselectivity. The change in stereoselectivity with decreasing acceptor nucleophilicity is related to a change in reaction mechanism shifting from the SN2 side to the SN1 side of the reactivity spectrum. Carbohydrate acceptors are examined and the reactivity–selectivity profile of these nucleophiles mirrored those of the model acceptors studied. The set of model ethanol acceptors thus provides a simple and effective “toolbox” to investigate glycosylation reaction mechanisms and report on the robustness of glycosylation protocols.

Graphical abstract: The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

Supplementary files

Article information

Article type
Edge Article
Submitted
17 Oct 2016
Accepted
08 Nov 2016
First published
09 Nov 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 1867-1875

The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

S. van der Vorm, T. Hansen, H. S. Overkleeft, G. A. van der Marel and J. D. C. Codée, Chem. Sci., 2017, 8, 1867 DOI: 10.1039/C6SC04638J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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