Investigations into the role of oxacarbenium ions in glycosylation reactions by ab initio molecular dynamics

We present a constrained ab initio molecular dynamics method that allows the modeling of the conformational interconversions of glycopyranosyl oxacarbenium ions. The model was successfully tested by estimating the barriers to ring inversion for two 4-substituted tetrahydropyranosyl oxacarbenium ions. The model was further extended to predict the pathways that connect the 4H3 half-chair conformation of 2,3,4,6-tetra-O-methyl-d-glucopyranosyl cation to its inverted 5S1 conformation and the 4H3 half-chair conformation of 2,3,4,6-tetra-O-methyl-d-mannopyranosyl cation to its inverted 3E conformation. The modeled interconversion pathways reconcile a large body of experimental work on the acid-catalyzed hydrolysis of glycosides and the mechanisms of a number of glucosidases and mannosidases.

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