No abstract

The nucleosides modified in the 2’- and/or 3’-position have been known for years and include important, bioactive compounds such as zidovudine, cytarabine, didanosine, puromycin, and fludarabine. This group consists of analogs with altered configuration, 2’,3’-dideoxy and 2’,3’-dideoxy-didehydro nucleosides, as well as derivatives with additional substituents. These compounds are often targeted against viruses and tumors. The sugar-base anhydro nucleosides have been known since the middle of the 20th century. However, their application has not yet been fully explored and described. The number of 2’,3’-dimodified derivatives, obtainable through sugar-base anhydrocyclic synthons, could be vast, especially taking into consideration various combinations of S-alkyl, S-aryl, O-alkyl, O-aryl, halogen, triazole, amine and azide substituents in both pyrimidine and purine nucleosides. Furthermore, application of anhydrocyclic structures can be an efficient method of introducing isotope labeled groups. The aim of this article is to provide an overview of the known methods of functionalization of the 2’- and/or 3’-position of nucleosides, using anhydrocyclic structures, and also to present a future outlook for this subject.

Mitsunobu reaction of partially acylated uridine proceeds with high regioselectivity for intramolecular SN2 anhydro linkage closuring. Under the reaction conditions, an isomeric mixture of diacyl uridine derivatives with either free 2'- or 3'-hydroxyl group was transformed into a single cyclonucleosidic product, 2,2'-anhydro-3',5'-di-O-acyluridine. This paper presents a possible mechanism of the reactions, the explanation of observed phenomenon based on semiempirical and density functional theory (DFT) calculations and possible utility of this synthetic pathway.