Syntheses and properties of novel conformationally restrained nucleoside analogues

This account describes our syntheses and conformational analyses of the bicyclic nucleoside analogues, 3'-O,4'-C-methyleneribonucleosides (4-BC), 3'-amino-3'-deoxy-3'-O,4'-C-methyleneribonucleosides (aza 4-BC), 2'-O,4'-C-methyleneribonucleosides (5-BC), and 3'-amino- and 3'-azido-3'deoxy-2'-O,4'-C-methyleneribonucleosides (aza 5-BC). The nucleoside analogues (4-BC and 5-BC) were effectively introduced into oligonucleotides by using a DNA synthesizer. Furthermore, unprecedented hybridizing ability towards complementary RNA and DNA, potent triplex-forming ability, and sufficient enzymatic stability of these modified oligonucleotides were also confirmed. From these studies, we believe that these conformationally restrained nucleoside analogues are good candidates for practical antisense/antigene molecules.