Liquid-Phase Synthesis of N-Functionalized Azanucleoside-Incorporated Oligonucleotides and Development of Anodic C(sp3)–H Acetoxylation Reaction for Direct Preparation of Azaribose
Liquid-Phase Synthesis of N-Functionalized Azanucleoside-Incorporated Oligonucleotides and Development of Anodic C(sp3)–H Acetoxylation Reaction for Direct Preparation of Azaribose
复制标题
N-功能化氮杂核苷掺入寡核苷酸的液相合成以及直接制备氮杂核糖的阳极 C(sp3)–H 乙酰氧基化反应的开发
作者：
K. Okamoto;Naoki Shida;M. Tsutsui;K. Chiba
摘要本文报道了芘偶联的氮杂核苷掺入寡脱氧核苷酸（aza-ODNs）的合成。通过烷基链可溶性载体（ACSS）的液相合成和电化学C-H活化的组合实现了高效获得aza-ODNs，而不需要过量的试剂或溶剂。并对芘偶联的氮杂寡核苷酸的荧光性质进行了研究。荧光光谱分析表明，对氮原子位置的修饰适合于人工功能化寡核苷酸的制备。azaribose作为aza-ODNs的前体，也重新研究了合成路线，以实现更有效的生产。发现在0.1M高氯酸锂/硝基甲烷/50 mM AcOH介质中的电化学N-α-乙酰氧基化是该路线的合适介质。这些结果代表了一种新的高效合成aza-ODNs的途径。
Abstract We report the synthesis of pyrene-conjugated azanucleoside-incorporated oligodeoxynucleotides (aza-ODNs). Combination of liquid-phase synthesis by alkyl-chain-soluble-support (ACSS) and electrochemical C–H activation realized efficient access to aza-ODNs without requiring an excess amount of reagent or solvent. The fluorescent properties of pyrene-conjugated aza-ODNs were also investigated. The resulting fluorescence spectrum indicated that the modification of the position of the nitrogen atom was suitable for the preparation of artificial functionalized oligonucleotides. A synthetic route to azaribose, as a precursor of aza-ODNs, was also reinvestigated to realize more efficient production. Electrochemical N-α-acetoxylation in 0.1 M lithium perchlorate/nitromethane/50 mM AcOH medium was found to be a suitable medium for this route. These results represent a new efficient synthetic route to aza-ODNs.