Fluorinated Carbohydrates as Potential Plasma Membrane Modifiers. Synthesis of 3-Deoxy-3-fluoro Derivatives of 2-Acetamido-2-deoxy-D- hexopyranoses.

Abstract 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.