The anomeric arylthio group and the hydroxyl-protecting groups of thioglycosides were optimized to construct carbohydrate building blocks for automated electrochemical solution-phase synthesis of oligoglucosamines having 1,4-β-glycosidic linkages. The optimization study included density functional theory calculations, measurements of the oxidation potentials, and the trial synthesis of the chitotriose trisaccharide. The automated synthesis of the protected potential N,N,N-trimethyl-d-glucosaminylchitotriomycin precursor was accomplished by using the optimized building block.

The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block.

Mixed electrolytes such as tetrabutylammonium triflate (Bu4NOTf) and tetrabutylammonium bis(trifluoromethanesulfonyl‐amide) (Bu4NNTf2) were found to improve stereoselectivity in electrochemical glycosylation of thioglycosides building blocks without a stereocontrolling group. Bu4NOTf was crucial to generate glycosyl triflate intermediate, whereas a second electrolyte such as Bu4NNTf2 contributes reducing solution resistance. Therefore, we assume that Bu4NOTf works as a reservoir of the triflate anion of the glycosyl triflate intermediate and Bu4NNTf2 works only as an electrolyte.

A benzyl‐ether‐type ionic‐liquid tag (IL tag) was developed and applied for electrochemical glycosylation. The IL tag was shown to display multifunctional roles in the glycosylation: the tag in thioglycosides worked as both an intramolecular electrolyte for the anodic oxidation and a stereo‐controlling group; it also enabled easy extraction of the products after the reaction.

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