Organic Chemistry

Accelerated Solid Phase Glycan Synthesis ASGS

Authors

Abstract

Solid phase synthesis is the most dominant approach for the synthesis of biological oligomers as it enables the introduc-tion of monomers in an iterative, reproducible manner. Solid phase synthesis of oligosaccharides is crucial for the devel-opment of glycobiology. Accelerated solid phase synthesis of biological oligomers is crucial for chemical biology, but its application to the synthesis of oligosaccharide is not trivial. Solid phase oligosaccharide synthesis is performed in a variety of conditions and temperatures, requires inert gas atmosphere, and demand high excess of glycosyl donors. The reactions are usually very long, and the poor mixing of the solid support increases the risk of diffusion-independent hydrolysis of the activated donor. The entire process is slow and done mostly in special synthesizers. High shear stirring is a new con-cept in solid phase that enables shortening the synthesis time. The efficient mixing makes sure that reactive intermedi-ates can diffuse faster to and into the solid support thereby increase the kinetics of the reactions. We report the first stir-ring-based accelerated solid-phase oligosaccharide synthesis. We harnessed high shear mixing to promote diffusion-dependent glycosylation over diffusion-independent side reactions resulting in high conversion in short reaction time. We eliminated the need for high excess of glycosyl donors and overcame the need to use inert atmosphere. We showed that by tailoring the deprotection and glycosylation conditions to the same temperature, all steps are performed continuously and full glycosylation cycles is completed in few minutes

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