Tuberculosis (TB) has been one the most infectious and deadly diseases for decades and is nowadays responsible for the death of 1.7 M people annually. The thick hydrophobic cell wall of the microorganism responsible for TB, Mycobacterium tuberculosis (M.tb), is the main reason for its persistence, creating an impermeable barrier for antibiotics.Two interesting constituents of this cell wall and only present in M.tb are acyl2sulfoglycolipid (Ac2SGL) and sulfolipid-1 (SL-1). Ac2SGL was recognized to function as an antigen, able to activate T-cells which in turn can release interferon-?, kill mycobacteria in vitro and recognize M.tb infected antigen presenting cells. The exact role of SL-1 is not yet known, although there are reports which associate it with the virulence of TB. To elucidate their exact structure and function we report the first complete synthesis of both.The branched fatty acids acylated at varying positions of the trehalose core were synthesized by means of an iterative protocol. This protocol relies on the highly selective copper-catalyzed 1,4-addition of Grignard reagents to alpha,beta-unsaturated thioesters. Regioselective acylation of the acids was obtained by a protection/deprotection sequence. To minimize the purification of highly polar intermediates the synthesis was planned in such a way that all protecting groups could be removed in a single final step. In the presentation we will discuss the strategy used and highlight the crucial steps in our synthesis.

Total synthesis of Ac<sub>2</sub>SGL and sulfolipid-1: Two 1,3-methyl branched sulfoglycolipids from mycobacterium tuberculosis

243rd National Meeting (2012)

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Total synthesis of Ac2SGL and sulfolipid-1: Two 1,3-methyl branched sulfoglycolipids from mycobacterium tuberculosis

Total synthesis of Ac₂SGL and sulfolipid-1: Two 1,3-methyl branched sulfoglycolipids from mycobacterium tuberculosis