Synthesis of some 5-halogenovinyl derivatives of uracil and their conversion into 2′-deoxyribonucleosides

Abstract

Treatment of 5-formyluracil with malonic acid in the presence of piperidine gave (E)-5-(2-carboxyvinyl)uracil which, upon reaction with the appropriate N-halogenosuccinimide, gave (E)-5-(2-bromovinyl)uracil, (E)-5-(2-chlorovinyl)uracil, and (E)-5-(2-iodovinyl)uracil. The last mentioned compound was also obtained by the action of iodine chloride on 5-vinyluracil. 5-(1-Chlorovinyl)uracil upon treatment with bromine gave 5(2-bromo-1-chlorovinyl)uracil which reacted with sodium methoxide to give 5-bromoethynyluracil. (E)-5-(2-Bromovinyl)-uracil was converted into into its trimethylsilyl derivative which was condensed with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride to give the α- and β-anomers of the blocked deoxyribonucleoside. Removal of the p-toluoyl blocking groups with sodium methoxide afforded (E)-5-(2-bromovinyl)-1-(2-deoxy-α-D-erythro-pentofuranosyl)uracil and (E)-5-(2-bromovinyl)-2′-deoxyuridine. A similar series of reactions gave (E)-5-(2-iodovinyl)-2′-deoxyuridine and 5-(2-bromo-1-chlorovinyl)-2′-deoxyuridine. 5-(1-Chlorovinyl)uracil could be condensed similarly with the blocked sugar derivative to give the α- and β-anomers of the blocked deoxyribonucleoside. Attempted removal of the groups with sodium methoxide gave 2′-deoxy-5-ethynyluridine and mild treatment with methanolic ammonia gave the same product and some 2′-deoxy-5-ethynyl-5′-O-(p-toluoyl)-uridine. 5-(1-Chlorovinyl)-2′-deoxyuridine was obtained by the addition of HCl to 2′-deoxy-5-ethynyluridine. Aspects of the elimination reactions of 5-(halogenovinyl)uracil derivatives are discussed.