Synthesis and antiviral evaluation of novel conformationally locked nucleosides and masked 5′-phosphate derivatives thereof

摘要

As part of a programme towards evaluating the potential of conformationally locked 3u0001-deoxy- and 3u0001-azido-3u0001-ndeoxy-nucleoside derivatives as prodrugs of potential 5u0001-O-triphosphorylated anti-HIV drugs, novel nucleosidenderivatives with locked N-type (north-type, C3u0001-endo) furanose conformation were prepared using convergentnsynthetic strategies. In addition, masked 5u0001-monophosphate derivatives of these, and of a conformationally restrictedn3u0001-azido-3u0001-deoxynucleoside with E-type (eastern-type, O4u0001-endo) furanose conformation, were prepared in order tonpotentially circumvent the first phosphorylation step. However, neither the free 5u0001-hydroxy derivatives nor the maskedn5u0001-monophosphates showed anti-HIV activity in MT-4 cells.