Rapid, iterative assembly of octyl alpha-1,6-oligomannosides and their 6-deoxy equivalents.

School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia 3010.

Organic & biomolecular chemistry 2005 May 21

filter terms:

Mycobacterium tuberculosis is the cause of the deadly human disease tuberculosis. In studies over the last 40 years it has been revealed that this organism possesses a complex cell wall including glycophospholipids such as the phosphatidylinositiol mannosides (PIMs), lipomannan (LM) and lipoarabinomannan (LAM). These glycolipids all contain a common alpha-1,6-linked mannoside core, and the higher PIMs and LAM possess alpha-1,2-linked mannosyl residues. It has been shown that simple alpha-1,6-linked oligomannosides can act as substrates for alpha-1,6-mannosyltransferases in mycobacteria. Here we report a simple iterative synthesis of a series of hydrophobic octyl alpha-1,6-linked oligomannosides from mono- through to tetrasaccharides. We have utilized a single thioglycoside donor and alcohol acceptor. Further, we have developed conditions for the conversion of each of these compounds to the 6-deoxy congeners. Deoxygenation of the 6-position of the terminal mannosyl residue should prevent these compounds acting as substrates for the abundant alpha-1,6-mannosyltransferases in mycobacteria and should permit detection of the elusive alpha-1,2-mannosyltransferase activity responsible for elaboration of LM to mature LAM and the biosynthesis of the higher PIMs.

Citation

Jacinta A Watt, Spencer J Williams. Rapid, iterative assembly of octyl alpha-1,6-oligomannosides and their 6-deoxy equivalents. Organic & biomolecular chemistry. 2005 May 21;3(10):1982-92