Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 4- and 6-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses

Carbohydr Res. 1990 May 1;198(2):205-21. doi: 10.1016/0008-6215(90)84293-4.

Abstract

2-Amino-2,4-dideoxy-4-fluoro- and 2-amino-2,4,6-trideoxy-4, 6-difluoro-D-galactose, and 2-amino-2,4-dideoxy-4-fluoro- and 2-amino-4-deoxy-4, 4-difluoro-D-xylo-hexose were synthesized, as potential modifiers of tumor cell-surface glyco-conjugate, from benzyl 2-acetamido-3-O-benzyl-2-deoxy-4, 6-di-O-mesyl-alpha-D-glucopyranoside and benzyl 2-acetamido-3, 6-di-O-benzyl-2-deoxy-4-O-mesyl-alpha-D-glucopyranoside, which were converted into the corresponding 4,6-difluoro-2,4, 6-trideoxy and 2,4-dideoxy-4-fluoro derivatives. Benzyl 2-acetamido-2-deoxy-4-O-mesyl-alpha-D-galactopyranoside and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-xylo-hexo-4-ulopyra noside were treated with diethylaminosulfur trifluoride to give 2-amino-2,4-dideoxy-4-fluoro-D-glucose and 2-amino-2,4-dideoxy-4, 4-di-fluoro-D-xylo-hexose derivatives, respectively, to give after deprotection the target compounds. Several of the peracetylated sugar derivatives inhibited L1210 tumor-cell growth in vitro at concentrations of 1-5 10(-5) M. The peracetylated derivative of 2-amino-2,4-dideoxy-4-fluoro-D-galactose inhibited protein and glycoconjugate biosynthesis, and also exhibited antitumor activity in mice with L1210 leukemia.

Publication types

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

MeSH terms

  • Acetylgalactosamine / analogs & derivatives*
  • Acetylgalactosamine / chemical synthesis
  • Acetylgalactosamine / pharmacology
  • Acetylglucosamine / analogs & derivatives*
  • Acetylglucosamine / chemical synthesis
  • Acetylglucosamine / pharmacology
  • Animals
  • Cell Count
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Chemical Phenomena
  • Chemistry
  • Fluorine
  • Galactosamine / analogs & derivatives*
  • Glucosamine / analogs & derivatives*
  • Mice
  • Tumor Cells, Cultured

Substances

  • Fluorine
  • Galactosamine
  • Acetylgalactosamine
  • Glucosamine
  • Acetylglucosamine