Skeletal Transformations\nObserved in the Reaction\nof a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

Some intriguing skeletal transformations were observed\nin the reaction\nof α-hydroxypyrrolidine thymine nucleoside <b>2</b> with\ndifferent dicarbonyl compounds. In these reactions, unusual ring systems,\ntogether with new C–C bonds and stereogenic centers of defined\nconfiguration, were formed in a single step. These reactions were\ninitiated by the nucleophilic attack of the NH of the pyrrolidine\nring, present on <b>2</b>, on one of the carbonyl moieties of\na dicarbonyl reagent and seem to proceed through an enamine–iminium\nmechanism. The present methodology is particularly attractive because\nno catalyst or aggressive conditions are needed. The new polycyclic\nnucleosides obtained from <b>2</b> can be good scaffolds for\ndiversification. In fact, modification and derivatization can be achieved\nby performing further chemical transformations of the functional groups\npresent in some of them. This may lead to the formation of new highly\nfunctionalized nucleosides. Our results show the high synthetic potential\nof <b>2</b> to construct complex systems in an efficient way.\nOn the other hand, the enamine chemistry involved in the particular\nreactivity of the α-hydroxy pyrrolidine ring present in <b>2</b> has no connection with the nucleobase and could be extended\nto simple glycosides preserving this essential ring system.