Over the last 5 years a number of very promising strategies for the solid support synthesis of oligosaccharides and glycoconjugates have been developed. Several of the glycosylating reagents successfully used in solution have yielded promising results under the soild phase paradigm. While a number of different solid support matrices and linkers have been explored, much work in this area remains to be done. The rapid developments in combinatorial chemistry on the solid support have created novel support matrices, which will find application to solid phase oligosaccharide synthesis. Innovative linkers will be required to allow for the use of highly flexible protecting group strategies in the synthesis of branched oligosaccharides.
Given the progress in the development of methods for the on-resin analysis of oligosaccharides, reaction development and optimization will be drastically accelerated. Novel glycosylating agents and orthogonal glycosylating schemes will further impact solid support synthesis. Alternative glycosylation methods such as the use of glycosyltransferase-catalyzed reactions on the solid support have also made great strides. For the synthesis of diverse structures, including natural and nonnatural gly-coconjugates, chemical synthesis will be of paramount importance.
While much progress has been made, many challenges remain before a flexible, high-yielding and absolutely selective strategy for the synthesis of oligosaccharides on the solid support becomes available. Once these problems have been solved, the construction of an automated oligosaccharide synthesizer may become feasible. Detailed studies concerning the structure and function of oligosaccharides and glyco-conjugates will be possible once rapid access to complex glycoconjugates is a reality.
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