Towards a Systematic Understanding of the Influence of Temperature on Glycosylation Reactions

Glycosidic bond formation is a continual challenge for practitioners. Aiming to enhance the reproducibility and efficiency of oligosaccharide synthesis, we studied the relationship between glycosyl donor activation and reaction temperature. A novel semi-automated assay revealed diverse responses of members of a panel of thioglycosides to activation at various temperatures. The patterns of protecting groups and the thiol aglycon combine to cause remarkable differences in temperature sensitivity among glycosyl donor building blocks. We introduce the concept of donor activation temperature to capture experimental insights, reasoning that glycosylations performed below this reference temperature evade deleterious side reactions. Activation temperatures enable a simplified temperature treatment and facilitate optimization of glycosyl donor usage. Isothermal glycosylation below the activation temperature halved the equivalents of building block required in comparison to the standard ramp regime used in solution- and solid-phase oligosaccharide synthesis to-date.

Automated summary

Research shows that glycosyl donor activation reactions at different temperatures exhibit diversity, and can avoid deleterious side reactions and reduce the amount of building blocks required by using an activation temperature. This finding contributes to optimizing the usage of glycosyl donors and improving the efficiency of oligosaccharide synthesis.