Syntheses and properties of conformationally restrained nucleosides and oligonucleotides analogues

This review summarizes our efficient syntheses of novel bicyclic nucleoside analogues, 3'-O,4'-C-methyleneribonucleosides (1) (4-BC type nucleoside an alogue), 2'-O,4'-C-methyleneribonucleosides (2) (5-BC), 3'-amino-3'-deoxy-3 '-N,4'-C-methyleneribonucleosides (3) (aza 4-BC), and 3'-azido- and 3'-amin o-3'-deoxy-2'-O,4'-C-methyleneribonucleosides (4, 5) (aza 5-BC). From H-1-N MR and X-ray crystallographic analyses, the 4-BC and aza 4-BC type nucleosi de analogues (1, 3) were found to have a S-conformation predominantly, whil e the conformations of 5-BC and aza 5-BC type nucleoside analogues (2, 4, 5 ) were exclusively locked in N-form. The 4-BC and 5-BC type nucleoside anal ogues (1, 2) were effectively introduced into oligonucleotides using a DNA synthesizer. Furthermore, unprecedented hybridizing ability towards complem entary RNA and DNA, RNA selectivity, potent tripler forming ability, and su fficient enzymatic stability of these modified oligonucleotides were also c onfirmed. These results should reveal a promising route to the development of antisense/antigene methodology.