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Keywords:

Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, Organic Chemistry

Abstract:

In order to obtain compounds which would give 2'-deoxy-5-vinyluridine (VdUrd) by elimination under basic conditions, a series of 5-(1-substituted ethy1)uracil derivatives has been made. Attempts to obtain 5-(1-alkyl- or -aryl-sulphonyloxy) derivatives were unsuccessful because elimination to give the 5-vinyl derivatives was extremely easy. 5-(1-Acyloxyethyl) derivatives did not eliminate, but with aqueous alkali gave 5-(1-hydroxyethyl)uracil derivatives. Reaction of VdUrd with a series of arenethiols gave 5-(1-arylthioethyl) -2'-deoxyuridines. In the absence of radical inhibitors 5-(2-arylthiaethyl) -2'- deoxyuridines were the major products. The arylthio compounds were oxidized to the corresponding sulphoxides and sulphones. Treatment of these 5-(1-substituted) derivatives with potassium t-butoxide in dimethylformamide gave VdUrd. As expected the reaction rate was greatest with the compound which had the best leaving group. However, with aqueous alkali the compounds gave 2'-deoxy-5-(1-hydroxyethy1)uridine and at pH 7.6 at 37 °C they were stable. When N-3 of the uracil ring was alkylated the elimination was faster. The implication of this result for the mechanism of the elimination is discussed. Two of the compounds synthesized, namely 2'-deoxy-5-[1(-2,4,5-trichlorophenyIthio) - ethyl] uridine and 2'-deoxy-3-methyl-5- [ 1 -(2,4,5-trichlorophenylthio)ethyl]uridine, showed activity against vaccinia virus and murine L1210 leukaemia cells at a concentration of 30-40 μg/ml, and 2'-deoxy-5-[(2-phenylthio)ethyl] uridine, had activity against different strains of herpes simplex viruses types 1 and 2 at a concentration of 20 μg/ml. © 1987, The Royal Society of Chemistry. All rights reserved.