On the influence of solvent on the stereoselectivity of glycosylation reactions
Kevin M. Dorst, Olof Engström, Thibault Angles d’Ortoli, Hani Mobarak, Azad Ebrahemi, Ulf Fagerberg, Dennis M. Whitfield, Göran Widmalm
Abstract
Methodology development in carbohydrate chemistry entails the stereoselective formation of C-O bonds as a key step in the synthesis of oligo- and polysaccharides. The anomeric selectivity of a glycosylation reaction is affected by a multitude of parameters, such as the nature of the donor and acceptor, activator/promotor system, temperature and solvent. The influence of different solvents on the stereoselective outcome of glycosylation reactions employing thioglucopyranosides as glycosyl donors with a non-participating protecting group at position 2 has been studied. A large change in selectivity as a function of solvent was observed and a correlation between selectivity and the Kamlet-Taft solvent parameter π* was found. Furthermore, molecular modeling using density functional theory methodology was conducted to decipher the role of the solvent and possible reaction pathways were investigated.