Automated solid-phase synthesis of protected oligosaccharides containing beta-mannosidic linkages

Area of Science:

• Carbohydrate Chemistry
• Glycobiology
• Organic Synthesis

Background:

• Automated oligosaccharide synthesis is crucial for advancing glycobiology.
• Efficient and routine synthetic access to diverse carbohydrates is currently limited.
• Installing challenging glycosidic linkages, like beta-mannosidic bonds, requires specialized methods.

Purpose of the Study:

• To develop the first automated solid-phase synthesis of oligosaccharides containing beta-mannosidic linkages.
• To establish reliable methods for incorporating difficult glycosidic linkages into automated synthetic strategies.

Main Methods:

• Utilized carboxybenzyl mannoside building blocks as effective beta-mannosylation agents.
• Employed [(Triisopropylsilyl)oxy]-methyl ether (Tom) as an orthogonal protecting group for mannose C3 elongation.
• Separated desired oligosaccharides from stereoisomeric by-products using reverse-phase High-Performance Liquid Chromatography (HPLC).

Main Results:

• Achieved excellent conversion rates using the developed beta-mannosylation agents.
• Obtained good to moderate selectivities in the formation of the beta-mannosidic linkage.
• Demonstrated successful separation of target oligosaccharides from unwanted isomers via HPLC.

Conclusions:

• The described methods represent the first automated solid-phase synthesis of oligosaccharides with beta-mannosidic linkages.
• This advancement expands the range of carbohydrates accessible through automation, including many of biological significance.
• The developed strategy contributes to making complex carbohydrate synthesis more efficient and routine for glycobiology applications.