Synthesis of 4-deoxy-4-fluoro analogues of 2-acetamido-2-deoxy-D-glucose and 2-acetamido-2-deoxy-D-galactose and their effects on cellular glycosaminoglycan biosynthesis

4-Deoxy-4-fluoro analogues of 2-acetamido-2-deoxy-D-glucose and 2-acetamido -2-deoxy-D-galactose were synthesized and evaluated as inhibitors of hepati c glycosaminoglycan biosynthesis. 2-Acetamido-1,3,6-tri-O-acetyl-2,4-dideox y-4-fluoro-D-glucopyranose (16) exhibited a reduction of [H-3]GlcN and [S-3 5]SO4 incorporation into hepatocyte cellular glycosaminoglycans to 12 and 1 8%, respectively, of the control cells, at 1.0 mM. Similarly, 2-acetamido-1 ,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-D-gala (31) exhibited a reduction of [H-3]GlcN and [S-35]SO4 incorporation to 1 and 9%. respectively, of the co ntrol cells, at 1.0 mM. Unlike 16, 31 exhibited a reduction of [C-14]Leu in corporation into cellular protein to 57% of control cells, at 1.0 mM. (C) 2 000 Elsevier Science Ltd. All rights reserved.