RESUMO
Dihydropacidamycins having an antibacterial spectrum modified from that of the natural product pacidamycins and mureidomycins have been synthesized. Synthetic dihydropacidamycins with noteworthy antibacterial activity against wild-type and resistant Escherichia coli have been identified (MIC=4-8 microg/mL). Some dihydropacidamycins are shown to have activity against multi-resistant clinical strains of Mycobacterium tuberculosis. Compounds of this class are inhibitors of the cell wall biosynthetic enzyme, MraY.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Peptídeos/síntese química , Peptídeos/farmacologia , Nucleosídeos de Pirimidina/síntese química , Nucleosídeos de Pirimidina/farmacologia , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Bactérias Aeróbias Gram-Negativas/crescimento & desenvolvimento , HumanosRESUMO
We describe in this paper the synthesis of 1,2-di-O-acetyl-5-azido-3,5-dideoxy-alpha,beta-L-arabinofuranose, a carbohydrate donor that was used for the synthesis of 1-(5'-amino-3',5'-dideoxy-alpha-L-arabinofuranosyl)uracil, the nucleoside found in dihydropacidamycin D. The carbohydrate donor was also used for the synthesis of a set of new nucleosides that were introduced in new dihydropacidamycins. These compounds were tested for biological activity, and the results showed that uracil is the only base recognized by MraY.
