CHEMICAL SYNTHESIS OF A NEW MATERIAL OF ANTISENSE NUCLEIC ACID "2'-PHOSPHORYLATED RNAS" -DIRECTED TOWARD ITS BASIC STRUCTURAL STUDIES AND REGULATION OF EXPRESSION OF HIV VIRUS-

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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-dimethylethyl) 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 building units were utilized for the solid phase synthesis of 2'-phosphorylated uridylate derivatives. We could synthesize 2,4,6, and 10mers of 2'-phosphorylated 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 fragmets.