Stereocontrolled Solid-Phase Synthesis of Phosphorothioate Oligoribonucleotides Using 2鈥?O-(2-Cyanoethoxymethyl)-nucleoside 3鈥?O-Oxazaphospholidine Monomers
A method for the synthesis of P-stereodefined phosphorothioate oligoribonucleotides (PS-ORNs) was developed. PS-ORNs of mixed sequence (up to 12mers) were successfully synthesized by this method with sufficient coupling efficiency (94鈥?9%) and diastereoselectivity (鈮?8:2). The coupling efficiency was greatly improved by the use of 2-cyanoethoxymethyl (CEM) groups in place of the conventional TBS groups for the 2鈥?O-protection of nucleoside 3鈥?O-oxazaphospholidine monomers. The resultant diastereopure PS-ORNs allowed us to clearly demonstrate that an ORN containing an all-(Rp)-PS-backbone stabilizes its duplex with the complementary ORN, whereas its all-(Sp)-counterpart has a destabilizing effect.