Synthesis and conformation of 3′,4′-BNA monomers, 3′-O,4′-C-methyleneribonucleosides

In order to develop novel 2',5'-linked oligonucleotide analogues aimed for antivirus reagents and antisense/antigene oligonucleotides, novel nucleoside analogues, 3'-O,4'-C-methyleneribonucleosides (3',4'-BNA monomers) were synthesized via two synthetic routes. The first route starting from uridine utilized a regioselective ring-closure reaction of the 4'-C-(p-toluenesulfonyl)oxymethyluridine derivative. The second route involved a coupling reaction of 1,2,3-tri-O-acetyl-4-C-(p-toluenesulfonyl)oxymethylribofuranose derivative with nucleobases followed by oxetan-ring formation to afford the 3',4'-BNA monomers bearing all four nucleobases. By means of H-1 NMR, X-ray crystallography and computational analysis, the sugar puckering of the 3',4'-BNA monomers was found to be restricted in S-conformation (C-1'-exo-C-2'-endo puckering mode). (C) 2002 Elsevier Science Ltd. All rights reserved.