The development of automated solution-phase synthesis of oligosaccharides

Park, Gisun
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This dissertation introduces the development and scope of automated solution-phase oligosaccharide synthesis based on fluorous tags. Compared to previously developed solid-phase and one-pot strategies, the new automated solution-phase methodology offers a more versatile platform for various solution-phase reaction conditions, with lower amounts of donor building blocks wasted. In addition, the fluorous-tag assisted solid-phase extraction was shown to be robust enough for automated purification steps to eliminate excess reagents. The optimization process that was required to be taken into account when designing a program to construct the complex oligosaccharide compounds is described in detail. The optimized protocols for automated oligosaccharide synthesis were then applied to the construction of oligosaccharides associated with anthrax and cholera infection. Chemistry was developed that allowed the simultaneous automated synthesis of both the anthrax- and cholera-associated oligosaccharides. Finally, a solution to solve limitations of a single fluorous tag strategy is presented. A di-tagged saccharide molecule was synthesized and tested under conventional bench-top conditions to obtain information on its robustness as applied to a glucosamine monosaccharide. This initial work was then extended to the automation platform and compared to the original mono-tagged strategy. For direct comparison, the two fluorous tags were incorporated into the initial rhamnose building block and were successfully made robotically. A second fluorous protecting group and new donor strategy were also introduced into the automated platform, thereby expanding the scope of the reactions and building block possibilities for future studies. By introducing the development, application and alternative strategic examples, this dissertation offers a new convenient and robust synthetic method for oligosaccharide construction.

automation, carbohydrate, oligosaccharide, solution-phase, synthesis