$a Síntese de derivados da D-arabinose e investigação da sua atividade antifúngica

Abstract

The glucosamine-6-phosphate synthase is the enzyme that catalyses the conversion of D-frutose-6-phosphate to D-glucosamine-6-phosphate. This is the first step in the biochemical pathway leading to the formation of an activated form of N-acetyl-Dglucosamine, namely uridine 5-diphospho-N-acetyl-D-glucosamine. This nucleoside provides N-acetyl-D-glucosamine for biosynthesis of lipopolysacharides,peptideoglycans in bacteria and chitin in fungi, insects and crustaceans. As an enzyme participating in biosynthesis of important cell wall components, the glucosamine-6-phosphate synthase is essential for the fungi cells, and its importance for these ones was demonstrated by the deletion of its gene, that proved to be lethal. In this work, it is described the synthesis of D-arabinose derivatives, modified in C-1 and phosphorylated in C-5, as potential antifungals agents. These were designed, based on the structure of the transition state of the reaction catalyzed by this enzyme. The compounds designed, 5-O-diestilphosphoryl-E,Z-D-arabinose oxime, aswell as 2-(D-arabino-1,2,3,4-tetrahydroxybutyl)-5-metil-1,3,4-oxadiazole could not be achieved. The compound modified in C-1 with a tetrazole ring and phosphorylated in C-5 was achieved in five steps. The compound 5-(D-arabino-4-diethylphosphoryloxy- 1,2,3-trihydroxybutyl)-tetrazole, as well as the others compounds sinthesized were evaluated against fungi and bacteria, however neither of them were active against the microorganism tested.