The reemergence of the mycobacterial disease tuberculosis as a human threat has prompted interest in the development of new drugs for the treatment of this disease.   The major structural polysaccharide of the mycobacterial cell wall is an arabinogalactan (AG), which is linked to peptidoglycan.  The AG is composed of a linker disaccharide to which is attached a linear galactan with alternating β-(1→5) and β-(1→6) linkages of D-galactofuranose (Galf) units. Mycobacterial viability is dependent on the ability of the organism to biosynthesize the galactan and this, combined with the absence of Galf residues in humans, suggests that inhibitors of the galactosyltransferase (glfT, Figure 1) involved in galactan assembly are ideal drug candidates.  As part of a larger program directed toward the identification of glfT inhibitors, we have carried out one-pot synthetic methods for the preparation of Galf-containing oligosaccharides for use in mapping the substrate specificity of the enzyme. 

Figure 1.  Reaction catalyzed by glfT in the synthesis of mycobacterial galactan.