1. Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses.
- Author
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Sharma M, Bernacki RJ, Hillman MJ, and Korytnyk W
- Subjects
- Animals, Antineoplastic Agents chemical synthesis, Deoxyglucose chemical synthesis, Deoxyglucose pharmacology, Leukemia L1210 pathology, Methylation, Mice, N-Acetylneuraminic Acid, Rhamnose chemical synthesis, Rhamnose pharmacology, Sialic Acids biosynthesis, Tumor Cells, Cultured, Acetylglucosamine analogs & derivatives, Antineoplastic Agents pharmacology, Cell Membrane drug effects, Deoxyglucose analogs & derivatives, Rhamnose analogs & derivatives
- Abstract
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.
- Published
- 1993
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