FLUORINATED CARBOHYDRATES AS POTENTIAL PLASMA-MEMBRANE MODIFIERS - SYNTHESIS OF 4-FLUORO AND 6-FLUORO DERIVATIVES OF 2-ACETAMIDO-2-DEOXY-D-HEXOPYRANOSES

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 glycoconjugate, from benzyl 2-acetamido-3-O-benzyl-2-deoxy-4,6-di-O-mesyl-α-d-glucopyranoside and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-mesyl-α-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-α-d-galactopyranoside and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-d-xylo-hexo-4-ulopyranoside 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 10-5m. 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. © 1990.