| Oligosaccharides are key players in a number of biological recognition processes and their preparation has attracted the attention of synthetic chemists for many years. Although a number of glycosylation procedures are available, there is still a need for the development of glycosyl donors, particularly glycosyl donors that can be activated in the presence of other potential donors. Such compounds allow the efficient synthesis of oligosaccharides via orthogonal glycosylation protocols.; We discovered that hydrolytically stable glycosyl 2-pyridyl sulfones can be used as glycosylating agents. Reaction of a glycosyl 2-pyridyl sulfone with a glycosyl acceptor in the presence of samarium(III) affords glycosides in good to excellent yields. In addition, thio-glycosides are inert under these conditions and the sulfones do not react to the N-iodosuccinimide/silver triflate promoter system commonly used to activate thioglycosides. This selectivity allowed the synthesis of three oligosaccharides through the use of orthogonal glycosylation protocols.; Mycobacterium tuberculosis is the causative infectious agent of tuberculosis, a contagious disease of the human respiratory system which is well known for the havoc it has wreaked throughout human history. The unique structure of its cell wall has been fully characterized. The carbohydrate portion of the cell wall consists largely polymers of arabinose and galactose in their furanose form. Glycosyltransferases are responsible for the biosynthesis of these polymers, inhibition of these enzymes can retard mycobacterial cell wall synthesis and compromise the integrity of the cell wall. In addition, inhibitors of these enzymes are interesting leads to therapeutics of tuberculosis.; We designed and synthesized C-disaccharides as potential inhibitors of arabinosyltransferase of M. tuberculosis. Specifically, these C-disaccharides mimic the glycosyl acceptor substrate for the enzyme, but are inert to hydrolysis at physiological pH. These compounds are therefore predicted to be more suitable drug candidates than their glycoside parents. Efficient syntheses of these molecules are described. |
