Synthesis of 4-deoxy analogues of 2-acetamido2-deoxy-D-glucose and 2-acetamido-2-deoxy-D-xylose and their effects on glycoconjugate biosynthesis

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 bio synthesis. Methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside (11) s howed a reduction in [H-3]GlcN and [C-14]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-alpha,beta-D-xy lo-hexopyranoses (15), showed a reduction of [H-3]GlcN and [C-14]Leu incorp oration 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-beta-D-xyl o-hexopyranoside and 2-acetamido-1.3,6-tri-O-acetyl-2,4-dideoxy-alpha,beta- D-xylo-hexopyranoses, showed a greater inhibition of [H-3]GlcN and [C-14]Le u incorporation at 1 mM compared with their non-acetylated counterparts, bu t were toxic to hepatocytes at concentrations of 10 and 20 mM. Correspondin g derivatives of 2-acetamido-2,4-dideoxy-L-threo-pentopyranose showed no bi ological effect up to 20 mM, suggesting that the C-6 substituent is importa nt for the biological activity. (C) 2000 Elsevier Science Ltd. All rights r eserved.