Aso M, Ikeno T, Norihisa K, Tanaka M, Koga N, Suemune H
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
J Org Chem. 2001 May 18;66(10):3513-20. doi: 10.1021/jo015532s.
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.
我们设计了一种新型的自旋标记核苷，其带有一个直接引入到核碱基上的N-叔丁基氨氧基自由基。合成了含有氨氧基自由基的嘌呤和嘧啶核糖核苷，如1a-d、2、3和4，以研究核碱基上N-叔丁基氨氧基自由基的稳定性和行为。三-O-硅烷基化的6-氯嘌呤核糖核苷（5）经锂化后与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氧化所得的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），通过电子顺磁共振光谱法对其进行了确认。同样，自旋标记嘧啶（13、20和23）的前体通过对三-O-保护的嘧啶衍生物（9、18和21）进行位点选择性锂化，然后与MNP反应并脱保护来合成。一项电子顺磁共振研究表明，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。
