Synthesis and antileukemic activity of certain D-fucopyranosyl nucleosides

Abstract

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.