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

Carbohydr Res. 1993 Feb 24:240:85-93. doi: 10.1016/0008-6215(93)84174-5.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosamine* / analogs & derivatives*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Membrane / drug effects*
  • Deoxyglucose / analogs & derivatives*
  • Deoxyglucose / chemical synthesis
  • Deoxyglucose / pharmacology
  • Leukemia L1210 / pathology
  • Methylation
  • Mice
  • N-Acetylneuraminic Acid
  • Rhamnose / analogs & derivatives*
  • Rhamnose / chemical synthesis
  • Rhamnose / pharmacology
  • Sialic Acids / biosynthesis
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Sialic Acids
  • 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoroglucopyranose
  • methyl 2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-3-fluoromannopyranoside
  • Deoxyglucose
  • N-Acetylneuraminic Acid
  • Rhamnose
  • Acetylglucosamine