Facile synthesis of α-D-Araf-(1→5)-D-Galf, the linker unit of the arabinan to the galactan in Mycobacterium tuberculosis

Abstract

The arabinogalactan is a crucial constituent of the cell wall of mycobacteria. Both monosaccharides (arabinose and galactose) are found in the furanose configuration, absent in mammals. An efficient synthesis of α-D-Araf-(1→5)-D-Galf, the linker unit of the arabinan to the galactan, is described. The strategy relies on the use of a conveniently substituted D-galactono-1,4-lactone as a precursor of the reducing furanose ring. The glycosylation step was performed by the tin(IV) chloride promoted method using 1,2,3,5-tetra-O-benzoyl-α,β-D-arabinofuranose. The arabinose donor was obtained in a crystalline state in one step by benzoylation of arabinose in hot pyridine. Selective glycosylation of the exocyclic OH-5 was obtained in 75% yield to give 2,3,5-tri-O-benzoyl-α-D-arabinofuranosyl-(1→5)-2,6-di-O-pivaloyl-D-galactono-1,4-lactone. Reduction with disiamylborane gave the disaccharide synthon, useful for further glycosylations. Dec-9-enyl α-D-Araf-(1→5)-β-D-Galf, a convenient substrate for arabinofuranosyl transferases studies, was obtained by the trichloroacetimidate method of glycosylation.Key words: arabinofuranose, galactofuranose, Mycobacterium arabinogalactan, trichloroacetimidate, tin(IV) chloride.