Emma R. Palmacci

DEVELOPMENT OF AN AUTOMATED OLIGOSACCHARIDE SYNTHESIZER

Publisher Summary This chapter discusses an approach for the development of an automated oligosaccharide synthesizer. To meet the demand for molecular tools, new methods for the rapid production of carbohydrates are needed. Carbohydrates are the most stereochemically challenging class of biopolymers to prepare, and different methods have been developed to address their synthesis. In addition to traditional solution-phase chemical synthesis, three methods—enzymatic methods, orthogonal one-pot chemical methods, and automated solid-phase methods—have become increasingly popular for the construction of oligosaccharides. The chapter develops an automated solid-phase approach for the chemical synthesis of oligosaccharides. In this study, by using an acceptor-bound solid-phase glycosylation strategy in a specially designed instrument, poly α- (1 → 2) mannosides as large as a decasaccharide were synthesized. The use of glycosyl phosphates was demonstrated with the synthesis of a dodecamer phytoalexin elicitor b-glucan. During this investigation, high-resolution magic angle-spinning nuclear magnetic resonance (HR-MAS NMR) analysis was used as an on-resin analytical tool. The method described in the chapter is anticipated to have a significant impact on the field of oligosaccharide synthesis. Although there are still a number of challenges to overcome, the automated construction of glycosidic linkages is expected to allow for the preparation of a diverse set of carbohydrate for pharmaceutical and biochemical evaluation.

Automated synthesis of polysaccharides.

Publisher Summary Carbohydrate synthesis requires the installation of a new stereocenter during each elongation event. The major challenges in carbohydrate synthesis are two-fold: (1) how to control the stereochemistry of each newly formed glycosidic linkage and (2) how to incorporate various degrees of branching. This chapter discusses an automated synthesis method for carbohydrate production. This automated method provides a framework for exploring the potential reaction conditions while at the same time minimizing the amount of effort required to create complex carbohydrates. An automated solid-phase method necessitates a polymer support and a linker that are compatible with the reagents used in carbohydrate synthesis. When initiating a synthesis, the choice of glycosylating agent and protecting groups governs the selection of activating and deblocking reagents. The automated method described in the chapter has proven useful with glycosyl trichloroacetimidate and glycosyl phosphate building blocks. Temporary protecting groups, such as levulinate esters, silyl ethers, and acetate esters also are compatible with automation. Using this set of reagents can help in accessing majority of natural carbohydrate linkages.