Investigation of Neighboring Group Participation in 3,4-Diacetylated Glycosyl Donors in the Gas Phase.

ABSTRACT

A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each glycosidic linkage has one of two possible stereo-chemical geometries, α/ß or 1,2-cis/trans. An established approach to install 1,2-trans glycosidic bonds is neighboring group participation (NGP), mediated by a 2-O-acyl group. Extension of this intramolecular stabilization to nucleophilic groups located at more remote positions has also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy to characterize the molecular ions of monoacetylated sugar donors and showed how the strength of the stabilizing effect depends on the position of the participating ester group on the glycosyl donor ring as well as on its relative stereochemistry. In this work, we investigated glycosyl donors carrying two acyl groups. Using isotope labelling and isomer population analysis we were able to resolving spectra of isomeric mixtures and establish the relative contribution of individual species. We conclude that 3,4-diacetyl mannosyl donors exclusively form a dioxanium ion as a result of C-3 acyl stabilization. In contrast, the glucosyl and galactosyl cations form mixtures of C-3 and C-4 acyl participation products. Hence, the combination of isotope labeling and population analysis allows for the study of increasingly complex glycosyl cations.