Stereocontrolled Solid-Phase Synthesis of Phosphorothioate Oligoribonucleotides Using 2鈥?O-(2-Cyanoethoxymethyl)-nucleoside 3鈥?O-Oxazaphospholidine Monomers

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• 作者：Yohei Nukaga ; Kohei Yamada ; Toshihiko Ogata ; Natsuhisa Oka ; Takeshi Wada
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：September 21, 2012
• 年：2012
• 卷：77
• 期：18
• 页码：7913-7922
• 全文大小：419K
• 年卷期：v.77,no.18(September 21, 2012)
• ISSN：1520-6904

文摘

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.