Microfluidic Techniques for Oligosaccharide Synthesis

Several technologies have been used in combination with or in addition to solid-phase oligosaccharide synthesis as an alternative to the classical carbohydrate synthetic approach [63-65], Presented in the following text are summaries of important findings. More details concerning microfluidic systems and outcomes are described in Chapter 8. 

In addition to the glycosylation studies, oligosaccharides were prepared by combining a continuous-flow reactor and the fluorous-tag separation technique [63], Reaction conditions for glycosylation and deprotection were first optimized and then scaled up to produce various oligosaccharides in excellent yield. Perfluorinated 

SCHEME 7.3 Optimization of glycosylation reactions in a microreactor, (a) Mannosylation optimization by varying temperature and incubation time, (b) Mannosylation optimization by solvent effect, (c) Sialylation optimization by donor and activator concentration. 

Koichi Fukase et al. reported an example of oligosaccharide synthesis by combining microreactors and an isolation strategy called synthesis based on affinity separation (SAS) [72, 73], The glycosylation was carried out under continuous flow, and the mixture was directly sent to the stainless steel affinity column, and the flow channel was switched to wash the column with CH2C12. The labeled disaccharide was trapped in the column later to be eluted with a mixture of CH2C12 and methanol to obtain the isolated oligosaccharide product. 

The use of microfluidic systems in oligosaccharide synthesis is in its infancy and far from being automated. More extensive use and development of such systems will open up new ways to access high-throughput and combinatorial oligosaccharide libraries. 

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