Synthesis and antileukemic activity of certain d-fucopyranosyl nucleosides

Based upon previously discovered antileukemic properties of 9-β-d-fucopyranosyladenine (1) in cell culture, four new nucleosides containing naturally occurring bases have been prepared from d-fucose. α-d-Fucopyranose tetraacetate was condensed with the silylated bases in either acetonitrile or 1,2-dichloroethane with tin(IV) chloride as the catalyst. The intermediates blocked nucleosides were obtained in crystalline form and deacetylated with methanolic sodium methoxide. 1-β-d-Fucopyranosyluracil (8), 1-β-d-fucopyranosylthymine (9), 1-β-d-fucopyranosylcytosine (10) as the hydrochloride salt, and 7-β-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.