Synthesis of a-D-Araf-(1-5)-b-D-Galf-(1-5)-b-D-Galf-(1-6)-D-Galf, constituent of the Mycobacterium tuberculosis arabinogalactan

C. GALLO-RODRIGUEZ; L. GANDOLFI DONADÍO; R. M. DE LEDERKREMER

Whistler, Canada

Congreso; XXIII International Carbohydrate Symposium; 2006

National Research Council Canada

Mycobacterial diseases have reemerged in the last years because of the appearance of multi-drug resistant strains of Mycobacterium and the relation of tuberculosis with AIDS. Integrity of the mycobacterial cell wall is essential for viability of mycobacteria. One of the components of this unique cell wall is the arabinogalactan (AG), in which both arabinose and galactose are found in the furanose form, absent in mammals. The galactan region consists of alternating b-(1®5)- and b-(1®6)-linked D-Galf residues. The linear galactofuranose chain is branched at OH-5 with the arabinan chains a-attached.1 Thus, an a-D-Araf-(1-5)-D-Galf linkage anchors the arabinan component to the galactan structure. In our laboratory, we have already synthesized the decenyl glycosides of b-D-Galf-(1®6)-b-D-Galf-(1®5)-b-D-Galf, b-D-Galf-(1®5)-b-D-Galf-(1®6)-b-D-Galf and a-D-Araf-(1®5)-b-D-Galf, components of the arabinogalactan.2,3 In this work, we present a straightforward synthesis of a-D-Araf-(1®5)-b-D-Galf-(1®5)-b-D-Galf-(1®6)-D-Galf (1). Compound 1 and the precursor tetrasaccharide lactone are synthons for the construction of neoglycoconjugates.             Our strategy relied on the use of partially substituted D-galactono-1,4-lactones 3 and 5 as precursors of the reducing furanose rings. The starting material for the synthesis was disaccharide 2, easily obtained by glycosylation of 2,6-di-O-pivaloyl-D-galactono-1,4-lactone (3) with 1,2,3,5-tetra-O-benzoyl-a,b-D-arabinofuranose promoted by tin (IV) chloride.3 Activation of 2 via the trichloroacetimidate and further glycosylation with the lactone derivative 3 gave exclusively the product of b-condensation at the exocyclic OH-5 (74 %). Reduction of the trisaccharide lactone with DSB yielded the furanosic derivative 4. After imidate formation, further glycosylation of lactone derivative 5 afforded the corresponding tetrasaccharide lactone (44 %), which by reduction gave compound 1 (85 %).