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

被引：39
|
作者：
Nukaga, Yohei [1 ]
Yamada, Kohei [2 ]
Ogata, Toshihiko [1 ]
Oka, Natsuhisa [3 ]
Wada, Takeshi [1 ]
机构：
[1] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Kashiwa, Chiba 2778562, Japan
[2] Yamasa Corp, Choshi, Chiba 2880056, Japan
[3] Gifu Univ, Fac Engn, Dept Chem, Gifu 5011193, Japan
来源：
JOURNAL OF ORGANIC CHEMISTRY | 2012年 / 77卷 / 18期
关键词：
RNA-SYNTHESIS; CHEMICAL-SYNTHESIS; PROTECTING GROUPS; MODIFIED OLIGONUCLEOTIDES; 2'-HYDROXYL PROTECTION; STEREOCHEMICAL COURSE; BIOLOGICAL-ACTIVITY; RIBONUCLEOSIDES; THERAPEUTICS; PHOSPHORUS;
D O I：
10.1021/jo301052v
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
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 (94-99%) and diastereoselectivity (>= 98:2). The coupling efficiency was greatly improved by the use of 2-cyanoethoxymethyl (CEM) groups in place of the conventional TBS groups for the 2'-O-protection of nucleoside 3'-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.
引用
收藏
页码：7913 / 7922
页数：10
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