The Synthesis of Sulfated Carbohydrates Using a Sulfate Protecting Group Strategy

Abstract

Sulfated carbohydrates play key roles in a wide range of biological processes such as blood clotting, viral entry into cells, amyloidogenesis, neurite outgrowth, tumor growth and metastasis. However, their synthesis still remains a considerable challenge. A general approach to the synthesis of sulfated carbohydrates was examined in which sulfate group is incorporated at the beginning of the syntheses as a protected sulfodiester. Towards this end, a series of sulfuryl imidazolium salts (SIS), a new class of sulfating agents, was prepared and examined as reagents for incorporating 2,2,2-trichloroethyl-protected sulfate esters into monosaccharides. The SIS that contained a 1,2-dimethylimidazolium moiety proved to be a superior sulfating agent compared to SIS bearing no alkyl groups or bulkier alkyl groups on the imidazolium ring. Difficult O- and N- sulfations that required prolonged reaction times and a large excess of the SIS bearing a 1-methylimidazolium group were achieved in high yield and in less time when employing less than half the 1,2-dimethylimidazolium derivative. Efforts were then made to apply the sulfate protecting group strategy to the total synthesis of a class of chondroitin sulfate glycosaminoglycans. These studies revealed some of the limitations of the sulfate protecting group approach to the synthesis of sulfated oligosaccharides. Studies on the selective introduction and isomerization of the carbobenzyloxy protecting group into 2,3-diols of 4,6-O-benzylidene galactose derivatives are also reported.