Synthesis of 4-deoxy analogues of 2-acetamido-2-deoxy- d-glucose and 2-acetamido-2-deoxy- d-xylose and their effects on glycoconjugate biosynthesis

Abstract

4-Deoxy analogues of 2-acetamido-2-deoxy- d-glucose and 2-acetamido-2-deoxy- d-xylose were synthesized and evaluated as inhibitors of glycoconjugate biosynthesis. Methyl 2-acetamido-2,4-dideoxy-β- d- xylo-hexopyranoside ( 11) showed a reduction in [ 3H]GlcN and [ 14C]Leu incorporation into hepatocyte cellular glycoconjugates by 89 and 88%, of the control cells, respectively, at 20 mM, whereas the free sugars, 2-acetamido-2,4-dideoxy-α,β- d- xylo-hexopyranoses ( 15), showed a reduction of [ 3H]GlcN and [ 14C]Leu incorporation by 75 and 64%, respectively, at 20 mM. The acetylated analogues of 11 and 15, namely methyl 2-acetamido-3,6-di- O-acetyl-2,4-dideoxy-β- d- xylo-hexopyranoside and 2-acetamido-1,3,6-tri- O-acetyl-2,4-dideoxy-α,β- d- xylo-hexopyranoses, showed a greater inhibition of [ 3H]GlcN and [ 14C]Leu incorporation at 1 mM compared with their non-acetylated counterparts, but were toxic to hepatocytes at concentrations of 10 and 20 mM. Corresponding derivatives of 2-acetamido-2,4-dideoxy- l- threo-pentopyranose showed no biological effect up to 20 mM, suggesting that the C-6 substituent is important for the biological activity.