Moai Yoshihiro, Hiroaki Hidekazu, Obika Saoshi, Kodama Tetsuya
Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Aichi, Japan.
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Nucleosides Nucleotides Nucleic Acids. 2020;39(1-3):131-140. doi: 10.1080/15257770.2019.1675169. Epub 2019 Oct 12.
Synthesis of selenomethylene-locked nucleic acids nucleoside bearing an adenine base (SeLNA-A) was investigated. We first examined the stereoinversion reaction at 2'-positions of a 5',3'--TIPDS-protected 4'--(hydroxymethyl)ribosyladenine derivative to give the corresponding arabinosyladenine. After triflation, treatment of the arabinosyladenine derivative with a mixture of selenium and sodium borohydride in ethanol managed to construct the desired SeLNA skeleton. Finally, removal of TIPDS by treating with fluoride gave the SeLNA-A nucleoside. In this study, we found the heat-labile property of SeLNA-A. It is necessary to know more precise characteristics of SeLNA to achieve its oligonucleotides synthesis.
对带有腺嘌呤碱基的亚硒甲基锁定核酸核苷（SeLNA-A）的合成进行了研究。我们首先考察了5'，3'-TIPDS保护的4'-（羟甲基）核糖基腺嘌呤衍生物在2'-位的立体反转反应，以得到相应的阿拉伯糖基腺嘌呤。三氟甲磺酸酯化后，在乙醇中用硒和硼氢化钠的混合物处理阿拉伯糖基腺嘌呤衍生物，成功构建了所需的SeLNA骨架。最后，用氟化物处理除去TIPDS，得到SeLNA-A核苷。在本研究中，我们发现了SeLNA-A的热不稳定性质。为了实现其寡核苷酸合成，有必要了解SeLNA更精确的特性。
