ORGN 395

Nucleoside analogues bearing 2´-C-a-(hydroxyalkyl) and 2´-C-a-alkyl substitutes have numerous applications in RNA chemistry and biology. In particular they provide a strategy to probe the interaction between the 2´-hydroxyl group of RNA and water. To incorporate these nucleoside analogues into oligonucleotides for studies of the Group II intron (Gordon, P. M. et al. Chem. Biol. 2004, 11, 237), we synthesized four new phosphoramidite derivatives of 2´-deoxy-2´-C-a-(hydroxyalkyl)cytidine (1: R = -(CH₂)₃OH; 3: R = -(CH₂)₄OH) and 2´-deoxy-2´-C-a-alkylcytidine (2: R = -(CH₂)₂CH₃; 4: R = -(CH₂)₃CH₃) from uridine via 2´-C-a-allylation, followed by alkene and alcohol transformations. Phosphoramidites 1 and 2 were prepared from uridine in overall yields of 30% (ten steps) and 13% (eleven steps), respectively. Phosphoramidites 3 and 4 were synthesized from uridine in overall yields of 21% (thirteen steps) and 25% (fourteen steps), respectively.