Synthesis of acylated nucleosides and ribonic-1,4-lactones as inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH)

Abstract

The synthesis of a representative group of substituted nucleosides and ribonic-1,4-lactones as potential inhibitors of trypanosomal enzyme gGAPDH is described. The novel 5-acylribonic-1,4-lactones were easily obtained from ribonic lactone by a three-step procedure involving protection-deprotection protocols, in good overall yields. All compounds synthesized were subjected to inhibitory assay against gGAPDH, the most active being those carrying aromatic groups attached to the ribose ring. Other structural features responsible for the observed activities are also discussed.