CHEMICAL SYNTHESIS OF A NEW MATERIAL OF ANTISENSE NUCLEIC ACID"2"PHOSTHORYLATEDRNAS" DIRETED TOWARD IIS BASIC STRUCTRAL STUDIES AND REGULATION OF EXPRESSION OF HIV VIRUS-

今年，我们试图研究合成2 '-磷酸化RNA所需的新有机反应的发展。首先，我们发现双（2-氰基-1，1-二甲基乙基）磷酰基不仅可以作为2 ′-羟基的保护基，而且可以作为2 ′-磷酸酯基的前体。发现这种保护的磷酰基在用HF/Py在二氯甲烷中除去3 ′，5-环甲硅烷基保护基时非常稳定，并且不从3 ′-2 ′羟基官能团迁移。这一发现使我们实现了关键中间体的构建，即整个研究所需的2 '-磷酸化3'-磷酰胺单元。构建单元用于固相合成2 '-磷酸化吡啶衍生物。我们可以以良好的产率合成2，4，6和10聚体的2 '-磷酸化尿苷酸。他们被发现是耐酸性和碱性条件，以及酶消化脾磷酸二酯酶。特别是10聚体的NMR证实了其独特的结构。目前，我们正在研究这些新的核酸衍生物与靶DNA或RNA片段的结合能力。

This year, we have tried to study the development of new organic reactions required for the synthesis of 2'-phosphorylated RNAs. As the result, we have achieved the following results : First, we found that bis(2-cyano-1, 1-diamethylethyl)phosphoryl can be used not only as a 2'-hydroxyl protecting groups but also as a precursor of the 2'-phosphate group. This protected phosphoryl group was found to be quite stable upon removal of a 3', 5-cyclic silyl protecting group with HF/Py in dichloromethane and not to migrate from the 3'-2' hydroxyl functions. This finding led us to realize the construction of key intermediates, 2'-phosphorylated 3'-phosphoramide units which were required throughout this study. The builiding units were utilized for the solid phase synthesis of 2'-phosohorylated yridylate derivatives. We could synthesize 2, 4, 6, and 10mers of 2'-phosphorylated uridylated uridylates in good yields. They were found to be resistant to acid and alkaline conditions as well as enzymatic digestion with spleen phosphodiesterase. In particular, the 10 mer proved to have an unique structure as evidenced by NMR.At the present time, we are studying the binding ability of these new nucleic acid derivatives for target DNA or RNA fragments.