Synthesis of novel Bi-, Tri-, and tetracyclic nucleosides by reaction of a common cyclic enamine derived from TSAO-T with nucleophiles

We report here the efficient regio-and stereoselective synthesis of new polycyclic nucleosides using a common cyclic enamine (7) as the starting material. In fact, the reaction of 7, easily prepared by reaction of 5¢-O-Tosyl TSAO-T under basic nonnucleophilic conditions (potassium carbonate), with different classes of nucleophiles, for example, nitrogen-, oxygen-, sulfur-, and carbon-based nucleophiles, or with amino acids afforded, with total regio-and stereoselectivity, new bi-, tri-, and tetracyclic nucleosides. This straighforward route represents an original and unambiguously regio- and stereoselective pathway to these compounds. Some of these polycyclic nucleosides may be useful intermediates for a second series of reactions that may lead to the generation of structurally new nucleosides.We thank Susana Ruiz and Marı´a Jose´ Galeote for their excellent technical as- sistance. We thank the Ministry of Education of Spain for grants to C.C. and M.-C.B. The Spanish Ministerio de Ciencia y Tecnologı´a (Project SAF2003-07219-C02- 01) and the European Commission (Projects QLK2-CT- 2000-00291 and HPAW-CT-2002-90001) are acknowl- edged for their financial support.Peer reviewe