Synthesis of 2'-N-methylamino-2'-deoxyguanosine and 2'-N,N-dimethylamino-2'-deoxyguanosine and their incorporation into RNA by phosphoramidite chemistry.
Synthesis of 2'-N-methylamino-2'-deoxyguanosine and 2'-N,N-dimethylamino-2'-deoxyguanosine and their incorporation into RNA by phosphoramidite chemistry.
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2-N-甲基氨基-2-脱氧鸟苷和2-N,N-二甲基氨基-2-脱氧鸟苷的合成及其通过亚磷酰胺化学掺入RNA。
DOI：
10.1021/jo201364x
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Piccirilli,JosephA
中科院分区：
文献类型：
--
作者：
Dai,Qing;Sengupta,Raghuvir;Deb,ShirshenduK;Piccirilli,JosephA
The 2′-hydroxyl groups within RNA contribute in essential ways to RNA structure and function. Previously, we designed an atomic mutation cycle (AMC) that uses ribonucleoside analogues bearing different C-2′-substituents, including −OCH3, −NH2, −NHMe, and −NMe2, to identify hydroxyl groups within RNA that donate functionally significant hydrogen bonds. To enable AMC analysis of the nucleophilic guanosine cofactor in theTetrahymenaribozyme reaction and at other guanosines whose 2′-hydroxyl groups impart critical functional contributions, we describe here the syntheses of 2′-methylamino-2′-deoxyguanosine (GNHMe) and 2′-N,N-dimethylamino-2′-deoxyguanosine (GNMe2) and their corresponding phosphoramidites. The key step in obtaining the nucleosides involved SN2 displacement of 2′-β-triflate from an appropriate guanosine derivative by methylamine or dimethylamine. We readily obtained the GNMe2phosphoramidite and incorporated it into RNA. However, the GNHMephosphoramidite posed a significantly greater challenge due to lack of a suitable −2′-NHMe protecting group. After testing several strategies, we established that allyloxycarbonyl (Alloc) provided suitable protection for 2′-N-methylamino group during the phosphoramidite synthesis and the subsequent RNA synthesis. This work enables AMC analysis of guanosine’s 2′-hydroxyl group within RNA.
