Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses.
Treatment of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-allopyranoside with diethylaminosulfur trifluoride or of the 3-O-mesyl derivative with tetrabutylammonium fluoride gave the 2,3-unsaturated compound instead of the expected 3-deoxy-3-fluoro derivative. The latter was obtained when benzyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-mesyl-alpha-D-allopyran oside was treated with potassium fluoride. Methyl 2-azido-4,6-O-benzylidene-2-deoxy-alpha-D-altropyranoside was converted into the 2-acetamido- and 2-phthalimido-3-O-mesyl derivatives; when treated with fluoride nucleophile, these gave only the 2,3-aziridine derivative. However, treatment of the 2-azido-2-deoxy derivative with diethylaminosulfur trifluoride gave methyl 2-azido-2,3-dideoxy-3-fluoro-alpha-D-mannopyranoside which, after reduction, deprotection, and acetylation, gave the acetylated derivative of methyl 2-acetamido-2,3-dideoxy-3-fluoro-alpha-D-mannopyranoside in excellent yield. These acetylated 3-fluoro derivatives exhibited inhibition of cell growth of murine L1210 leukemia cells in culture at micromolar concentrations.
Sharma
M
M
Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263.
Bernacki
R J
RJ
Hillman
M J
MJ
Korytnyk
W
W
D000117:Acetylglucosamine / Q000031:analogs & derivatives*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007939:Leukemia L1210 / Q000473:pathology; D008745:Methylation; D051379:Mice; D019158:N-Acetylneuraminic Acid; D012210:Rhamnose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D012794:Sialic Acids / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012794:Sialic Acids; C080445:2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoroglucopyranose; C080446:methyl 2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-3-fluoromannopyranoside; D003847:Deoxyglucose; D019158:N-Acetylneuraminic Acid; D012210:Rhamnose; D000117:Acetylglucosamine