Some chemical reactions of 5-vinyluracil and 2′-deoxy-5-vinyluridine

Abstract

In an attempt to elucidate the chemical reactions responsible for the antiviral and toxic properties of 2′-deoxy-5-vinyluridine (1), the chemistry of some 5-vinyluracil derivatives has been studied. Under aqueous acidic conditions 5-vinyluracil (5) is in equilibrium with 5-(1 -hydroxyethyl)uracil (6) and the dimer, (E)-1,3-bis(uracil-5-yl)but-1-ene (9). The formation of (9) is favoured in concentrated solution. Upon treatment with aqueous acid compound (1) gives 2′-deoxy-5-(1-hydroxyethyl)uridine (4) but no dimerisation occurs. 1-Ethyl-5-vinyluracil (7) has been synthesized and this in hydrochloric acid gives the dimer, (E)-1,3-bis(1-ethyluracil-5-yl)but-1-ene (10). Under similar conditions compound (5) reacts with L-cysteine to give 5-(1-L-cystein-S-ylethyl)uracil (11) and with phenol to give a mixture of substituted phenols. Compound (1) reacts with butan-1-ol in the presence of trifluoroacetic acid to give 5-(1-butoxyethyl)-2′-deoxyuridine (14); under more vigorous conditions 5-(1-butoxyethyl)uracil (13) was formed. In 1 M hydrochloric acid at 100 °C compound (1) reacts with phenol to give a mixture of substituted phenols. From this mixture 2′-deoxy-5-[1-(4-hydroxyphenyl)ethyl]uridine (17) was isolated and characterised. In a similar manner compound (1) reacted with 4-propan-2-ylphenol to give 2′-deoxy-5-[1-(2-hydroxy-5-propan-2-ylphenyl)ethyl]uridine (18). Treatment of compound (1) with m-chloroperbenzoic acid in water–tetrahydrofuran gave 2′-deoxy-5-(1,2-dihydroxyethyl)uridine (19) which was characterised as its tetra-O-acetate (20).