Modifications at the C(5) position of pyrimidine nucleosides

Abstract

This review summarizes the state of knowledge on the chemical methods of C(5)-modifications of uridine and cytidine derivatives and may serve as a useful tool for synthetic chemists to choose an appropriate reaction protocol. The synthesis of 5-substituted uracil derivatives is gaining an increasing interest because of their possible applications in medicine and pharmacy. Modifications at the C(5) position of pyrimidine nucleosides can enhance their biostability, bioavailability or(and) biological activity. Among the C(5)-modified nucleosides, 5-halopyrimidines exhibit anticancer, antiviral, radio- and photosensitizing properties. Besides 5-halo-substituted derivatives, there are other examples of nucleosides with confirmed biological activity containing a C–C bond at the C(5) position in the pyrimidine ring. In recent decades, scientists have achieved great progress in the field of cross-coupling reactions. Among them, nickel-catalyzed processes provide a broad spectrum of synthetic methods that are based on less toxic and cheaper starting materials. This review summarizes the synthetic approaches based on the coupling or halogenation reactions, which enable 5-substituted pyrimidine nucleosides to be obtained. Moreover, the importance of the systems considered for medicine and pharmacy is briefly discussed. The bibliography includes 197 references.

Selection of Optimised Ligands by Fluorescence-Activated Bead Sorting

“…Step 2: Synthesis of modified monomers. We chose to modify the uridine (U) monomers at the C5 position since this is synthetically accessible, 33 and gives modifications of medical relevance 34,35,36 which would sufficiently validate our method. The modifications were designed to cover aryl (-Ph) and aliphatic hydrophobic (-Vi), halogenated (-I), and natural uridine (i.e.…”

5-(N-Trifluoromethylcarboxy)aminouracil as a Potential DNA Radiosensitizer and Its Radiochemical Conversion into N-Uracil-5-yloxamic Acid

“…5-Substituted uracils are by far the most common derivatives of uracil, due to the susceptibility of this position to chemical transformation. Besides halogenation reactions that lead to the C5–X bond (X = F, Cl, Br or I), other substituents can be relatively easily introduced into this nucleobase [ 27 ]. For instance, the amination reaction of 5-bromouracil may serve to obtain 5-aminouracil (NH 2 U).…”

Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

“…These techniques (grinding or milling) are a powerful strategy for the rapid, clean, and solvent-free synthesis of many biologically active compounds [168]. These reactions are usually performed in a mixer ball mill or mortar grinder and are of great value due to the possibility of reducing or completely eliminating the use of solvents, enhancing the conversion of substrates or even obtaining products that were unavailable with the previously used methods [169]. In addition, in many cases, the use of the above techniques allows for a significant reduction of reaction time and saving of synthesis costs.…”