Methodologies for the Rapid Synthesis of Hexoses and Their Application Towards a Differentially-Protected Chondroitin Sulfate Tetrasaccharide

Citation

Saliba, Katie Rose (2008) Methodologies for the Rapid Synthesis of Hexoses and Their Application Towards a Differentially-Protected Chondroitin Sulfate Tetrasaccharide. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/HWFJ-P813. https://resolver.caltech.edu/CaltechETD:etd-05292008-230310

Abstract

Carbohydrates play many roles in biology, but their study has been hindered by the paucity of methods available to rapidly access hexoses. In 2004, the MacMillan laboratory published a two-step aldol methodology that allows access to the erythrohexoses allose, glucose, and mannose. Described herein is the development of two methodologies to access hexoses. First, the two-step aldol methodology for accessing the erythrohexoses was expanded to allow access to a differentially-protected mannosamine and gulose. Also described is the discovery of a one-step aldol methodology for accessing hexoses, which has allowed access to a protected allose and gulose.

This methodology was applied to the synthesis of a differentially-protected chondroitin sulfate di- and tetrasaccharide. Chondroitin sulfate is a complex linear polysaccharide composed of alternating glucuronic acid and galactosamine residues that are heterogeneously sulfated. Combining the aldol methodology with a Cerny epoxide methodology developed in the Hsieh-Wilson laboratory, a core disaccharide was accessed. Model studies confirmed each position could be accessed selectively. Elaboration of this disaccharide to the protected tetrasaccharide was hindered by an unfavorable rearrangement during the tetrasaccharide coupling, so a second core disaccharide was synthesized. This core disaccharide was elaborated to a common intermediate to confirm that it should still allow selective access to each position, and then the disaccharide was elaborated towards the desired protected tetrasaccharide.

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