Synthesis and evaluation of 1,2-trans alkyl galactofuranoside mimetics as mycobacteriostatic agents.

ABSTRACT

The simple octyl ß-D-galactofuranoside was previously described as a good bacteriostatic agent against Mycobacterium smegmatis, a non-pathogenic model of M. tuberculosis. In order to decipher its mechanism of action, STD NMR on whole M. smegmatis cells was implemented. It outlined the crucial role of the alkyl chain and the possibility of modulation on the furanosyl entity. Then, 16 new alkyl furanosides were synthesized in order to optimize the mycobacteriostatic activity. They all present the pending alkyl chain in a 1,2-trans configuration relative to the sugar ring. Three families were studied that differ by a substituent on the primary position of the galactofuranose ring, the series or the pending alkyl chain. Four of these neofuranosides showed growth inhibition inferior to the parent octyl ß-D-galactofuranoside. Double alkyl chains at C-1 and a polar substituent on the primary position of the furanoside significantly favored the activity. Finally, a mixed biantennary alkyl/aryl ß-D-galactofuranoside exhibited the best growth inhibition concentration at 90 µM.