Carbohydrate research

Plausible Transition States for glycosylation reactions.

PMID 22525097


The Transition State (TS) for any chemical glycosylation reaction is not known with certainty. Both experimental and computational approaches have been limited due to the complexity of the problem. This work describes a preliminary computational ionization approach using density functional theory calculations to arrive at hypothetical TSs. The new TSs contain the glycosyl donor as anomeric triflates, the acceptor as methanol, some CH(2)Cl(2) molecules, and a Li(+) ion promoter. In this computational approach all glycosylations are disassociative in that the C-1-O(Tf) bond length is greater then 2 Å before any nucleophilic attack. All nucleophilic attack requires some preassociation of the nucleophile with examples of the pre-attack complexation to donor oxygens. These hypothetical models are intended to guide both experimental and computational approaches to finding TSs for glycosylation reactions that can be used to optimize stereoselectivity of glycosylation.