Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses

Article abstract of DOI:10.1016/0008-6215(93)84174-5

Treatment of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-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-α-D-allopyranoside was treated with potassium fluoride.Methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-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-α-D-mannopyranoside which, after reduction, deprotection, and acetylation, gave the acetylated derivative of methyl 2-acetamido-2,3-dideoxy-3-fluoro-α-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.