Synthesis and antileukemic activity of certain D-fucopyranosyl nucleosides.
Based upon previously discovered antileukemic properties of 9-beta-D-fucopyranosyladenine (1) in cell culture, four new nucleosides containing naturally occurring bases have been prepared from D-fucose. alpha-D-Fucopyranose tetraacetate was condensed with the silylated bases in either acetonitrile or 1,2-dichloroethane with tin(IV) chloride as the catalyst. The intermediate blocked nucleosides were obtained in crystalline form and deacetylated with methanolic sodium methoxide. 1-beta-D-Fucopyranosyluracil (8), 1-beta-D-fucopyranosylthymine (9), 1-beta-D-fucopyranosylcytosine (10) as the hydrochloride salt, and 7-beta-D-fucopyranosylguanine (11) were crystallized, and their structures were verified by spectroscopic techniques. Nucleosides 8 and 9 had only borderline activity against leukemia L1210 cells grown in culture, whereas nucleoside 11 had activity equal to 1. However, nucleoside 10 proved to be twice as active as either 1 or 11. The antileukemic activity, which was due to the inhibition of cell division, was reversible by transfer of the arrested cells to fresh media or by the addition of cytidine.
Lerner
L M
LM
Department of Biochemistry, State University of New York, Brooklyn 11203.
Mennitt
G
G
Gaetjens
E
E
Sheid
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009705:Nucleosides