Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butylaminoxyl radicals.
Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butylaminoxyl radicals.
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具有 N-叔丁基氨基氧基的新型自旋标记核糖核苷的分子设计。
DOI：
10.1021/jo015532s
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
H. Suemune
中科院分区：
文献类型：
--
作者：
M. Aso;T. Ikeno;K. Norihisa;M. Tanaka;N. Koga;H. Suemune
我们设计了一种新型自旋标记核苷，其带有直接引入核碱基的 N-叔丁基氨氧基自由基。合成了含有氨基氧基自由基（如 1a-d、2、3 和 4）的嘌呤和嘧啶核糖核苷，以研究 N-叔丁基氨基氧基自由基在核碱基上的稳定性和行为。三-O-甲硅烷基化的 6-氯嘌呤核糖核苷 (5) 锂化，然后与 2-甲基-2-亚硝基丙烷 (MNP) 反应，得到关键化合物 6a，其进一步转化为 6b-d。用 Ag(2)O 氧化获得的 6a-d 及其三醇 (7a-d) 导致形成相应的稳定自旋标记核苷（8a-d 和 1a-d），这一点通过 EPR 光谱证实。类似地，自旋标记嘧啶（13、20和23）的前体是通过三O-保护的嘧啶衍生物（9、18和21）的位点选择性锂化合成的，然后与MNP反应并脱保护。 EPR 研究表明氨氧基自由基（2、3 和 4）是稳定的，并且它们的超精细结构取决于自由基的位置。嘧啶的电子密度也影响超精细结构。
We designed a new type of spin-labeled nucleosides with an N-tert-butylaminoxyl radical which is introduced to the nucleobase directly. Purine and pyrimidine ribonucleosides containing the aminoxyl radical such as 1a-d, 2, 3, and 4 were synthesized to investigate the stability and behavior of the N-tert-butylaminoxyl radical on a nucleobase. Lithiation of tri-O-silylated 6-chloropurine ribonucleoside (5) followed by reaction with 2-methyl-2-nitrosopropane (MNP) gave the key compound 6a, which was further converted to 6b-d. Oxidation of the obtained 6a-d and their triols (7a-d) with Ag(2)O led to formation of the corresponding stable spin-labeled nucleosides (8a-d and 1a-d), which were confirmed by EPR spectroscopy. Similarly, the precursors of spin-labeled pyrimidines (13, 20, and 23) were synthesized by site-selective lithiation of tri-O-protected pyrimidine derivatives (9, 18, and 21) followed by the reaction with MNP and deprotection. An EPR study showed that the aminoxyl radicals (2, 3, and 4) were stable and that their hyperfine structures were dependent on the position of the radical. Electron densities of pyrimidine also affected hyperfine structures.