Skeletal Transformations Observed in the Reaction of a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

Some intriguing skeletal transformations were observed in the reaction of α-hydroxypyrrolidine thymine nucleoside 2 with different dicarbonyl compounds. In these reactions, unusual ring systems, together with new C-C bonds and stereogenic centers of defined configuration, were formed in a single step. These reactions were initiated by the nucleophilic attack of the NH of the pyrrolidine ring, present on 2, on one of the carbonyl moieties of a dicarbonyl reagent and seem to proceed through an enamine-iminium mechanism. The present methodology is particularly attractive because no catalyst or aggressive conditions are needed. The new polycyclic nucleosides obtained from 2 can be good scaffolds for diversification. In fact, modification and derivatization can be achieved by performing further chemical transformations of the functional groups present in some of them. This may lead to the formation of new highly functionalized nucleosides. Our results show the high synthetic potential of 2 to construct complex systems in an efficient way. On the other hand, the enamine chemistry involved in the particular reactivity of the α-hydroxy pyrrolidine ring present in 2 has no connection with the nucleobase and could be extended to simple glycosides preserving this essential ring system.