p-Tolyl 2,3,5-Tri-O-benzoyl-1-thio-α-D-arabinofuranoside: A Useful Thioglycoside Building Block in the Synthesis of Oligoarabinofuranosides

MAJU, JOE; YU, BAI; LUCÍA, GANDOLFI DONADÍO; TODD, L., LOWARY

Carbohydrate Chemistry, Proven Synthetic Methods Volume 1

TAYLOR AND FRANCIS GROUP LLC

Año: 2010; p. 341 - 347

Furanose residues are important constituents of glycoconjugates of many bacterial,1 parasitical,2 fungal3 and plant species.4  Although many different organisms produce furanose-containing glycans, arguably the most impressive examples of such compounds are found in mycobacteria.1,5  This genus of bacteria contains a number of species, including the well-known human pathogens Mycobacterium tuberculosis, Mycobacterium leprae and Mycobacterium ulcerans, the causes of tuberculosis, leprosy and buruli ulcer, respectively.  The cell wall of these organisms are composed in large part of two polysaccharides, arabinogalactan and lipoarabinomannan, a major component of both these molecules is a D-arabinofuranan moiety.5  It has been known for several years that the clinically used anti-tuberculosis agent, ethambutol, acts by inhibiting the action of at least one of the arabinofuranosyltransferases involved in mycobacterial arabinan biosynthesis.6  This discovery, and the need for developing new anti-tuberculosis agents due to the emergence of drug resistant M. tuberculosis strains,7 has led to heightened interest in the chemistry and biochemistry of arabinofuranose residues.8  In particular, the identification of arabinofuranosyltransferase inhibitors has received increasing attention.9  Given the xenobiotic nature of arabinofuranose-containing glycans in humans, the biosynthetic pathways leading to the formation of mycobacterial D-arabinan are believed to be attractive targets for drug action.9,10   However, the processes by which these polysaccharides are assembled are not well understood, and much additional research in this area is needed before new potent inhibitors of these enzymes can be identified.9,10  Such studies, in turn, require synthetic substrates that can be used for fundamental biochemical studies leading to the characterization of the appropriate biosynthetic enzymes.11 In previous investigations, arabinofuranose thioglycosides have been used to assemble oligoarabinofuranosides11,12 and we describe here a 100 g scale synthesis of p-tolyl 2,3,5-tri-O-benzoyl-α-D-arabinofuranoside.13