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 hepatic glycosaminoglycan biosynthesis. 2-Acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-D-glucopyranose (16) exhibited a reduction of [3H]GlcN and [35S]SO4 incorporation into hepatocyte cellular glycosaminoglycans to 12 and 18%, respectively, of the control cells, at 1.0 mM. Similarly, 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-D-galactopyranose (31) exhibited a reduction of [3H]GlcN and [35S]SO4 incorporation to 1 and 9%, respectively, of the control cells, at 1.0 mM. Unlike 16, 31 exhibited a reduction of [14C]Leu incorporation into cellular protein to 57% of control cells, at 1.0 mM.
Berkin
A
A
Department of Chemistry, Queen's University, Kingston, Ont., Canada.
Szarek
W A
WA
Kisilevsky
R
R
D000116:Acetylgalactosamine / Q000031:analogs & derivatives; D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D014176:Protein Biosynthesis
C416966:2-acetamido-1,3,6-tri-O--acetyl-2,4-dideoxy-4-fluoro-D-glucopyranose; C416965:2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-D-galactopyranose; D006025:Glycosaminoglycans; D000116:Acetylgalactosamine; D000117:Acetylglucosamine; D005690:Galactose