Oligosaccharide automated synthesis

SCHEME 7.2 The first solid-supported oligosaccharide synthesis. Bn, benzyl. 

Advances in solid-phase oligosaccharide synthesis led to the development of an automated platform that was first demonstrated by Peter Seeberger and coworkers in 2001 using a modified peptide synthesizer [38], Automated washing, deprotection, and glycosylation steps dramatically reduced the time and labor usually attributed to solution- and solid-phase synthesis of oligosaccharides. 

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While no examples of automated solid-phase oligosaccharide synthesis had been reported until the work described here,2 automated oligosaccharide synthesis was predated by efficient methods for the synthesis of peptides3 and nucleic acids.4 Here we briefly discuss the general features of each method, with particular emphasis on the scale and efficiency of peptide and nucleic acid synthesis. 

David Crich [56], elongation of complex p-mannose-containing oligosaccharides (e.g., 10) was demonstrated [54], Apparently, new strategies for glycosidic bond formation can be readily transferred to automated oligosaccharide synthesis. 

Solid-phase oligosaccharide synthesis olfers good opportunities for automahon, and using a modihed pephde synthesizer automated oligosaccharide synthesis has been described [114]. As an example of automated ohgosaccharide synthesis, the preparation of the core pentasaccharide of A-hnked glycoproteins (223) is shown in Scheme 5.38 and Scheme 5.39 [115]. 

Although of limited scope, one approach for solid phase carbohydrate synthesis has actually incorporated coupling chemistry into an automated solid phase oligosaccharidesynthe-sizer (123). In addition, there is the use of gly-cosyltransferase-regenerating beads that are potentially applicable to automated oligosaccharide synthesis (124). 

Figure 11 Automated oligosaccharide synthesis of GPI structure on solid phase. ...

Scheme 11.2-2 Automated oligosaccharide synthesis with glycosyl phosphates. Initial glycosylation of resin-bound acceptor produces a coupling product that may be subsequently deprotected. Iteration of coupling and deprotection cycles with phosphate donors 4-8 followed by cleavage of the resin-bound oligosaccharides and purification gives 1-3.

Automated Oligosaccharide Synthesis Using Fluorous Tags... 

In conclusion, compared with solution-phase synthesis, solid-phase enzymatic synthesis, generally, needs higher concentrations of enzyme, longer reaction times, and a large excess of donors. Although there is still room for improvement in terms of yields and scale-up of syntheses, in solid-phase synthesis purification procedures are straightforward so it is expected that this approach will open the route to automated oligosaccharide synthesis in the near future. 

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