Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 4- 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 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.
Sharma
M
M
Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Bernacki
R J
RJ
Paul
B
B
Korytnyk
W
W
D000116:Acetylgalactosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena; D002621:Chemistry; D005461:Fluorine; D005688:Galactosamine / Q000031:analogs & derivatives*; D005944:Glucosamine / Q000031:analogs & derivatives*; D051379:Mice; D014407:Tumor Cells, Cultured
D005461:Fluorine; D005688:Galactosamine; D000116:Acetylgalactosamine; D005944:Glucosamine; D000117:Acetylglucosamine