Advances in the synthesis of 5-and 6-substituted uracil derivatives

Abstract

The uracil unit is one of the most important structures in life, it being part of the building blocks of RNA and DNA and other natural products; therefore, it is not surprising that uracil derivatives have important biological activity. Uracil-based compounds are used in the treatment of cancer (5-fluoruracil) and against infections of the HIV virus (AZT). Actions as antiviral and antitumoral agents are perhaps the most widely reported activity. However, other uracil derivatives have been synthesized which are herbicides, insecticides, bactericides, acaricides, etc. In addition, uracil units can be found in the chemistry of peptide nucleic acid (PNA) or as part of other fused systems with antiallergic, antihypertensive, cardiotonic, bronchodilator or antibronchitis activity.The search for uracil derivatives has been carried out since the beginning of the last century and even today there is great interest in the development of new derivatives and strategies for synthesis so as to improve the yield of known compounds. To prepare uracils, there are three main synthetic strategies: a) building the uracil nucleus from acyclic precursors with appropriate substituents; b)modification of the structure of functionalized uracils or uracil itself by reaction with different reagents, as the recent synthesis of 5-trifluoromethyluracil and uridines with oxiranyl and tetrahydrofuranyl substituents; c) functionalization of masked uracil moieties with reactions incompatible with the nucleus, for example the synthesis of 6-aryl and 6- acyluracils and 2 -eoxypseudouridine. Combinations of these approaches are often found in the synthesis of target compounds with potential biological activities.The present review will cover advances in the synthesis of 5- and 6-substituted uracils over the last 8-10 years. This review has been organized in terms of the type of union that links the uracil moieties to the substitution groups; fused systems will have a separate section.