Novel fluoride-labile nucleobase-protecting groups for the synthesis of 3'(2')-O-amino-acylated RNA sequences

With the aim to develop a general approach to a total synthesis of amino-acylated t-RNAs and analogs, we describe the synthesis of stabilized, amino-acylated RNA fragments, which, upon ligation, could lead to amino-acylated t-RNA structures. Novel RNA phosphoramidites with fluoride-labile 2'-O-[(triisopropylsilyl)-oxy]methyl (=tom) sugar-protecting and N-{{2-[(triisopropylsilyl)oxy]benzyl}oxy}carbonyl (=tboc) base-protecting groups were prepd., as well as a solid support contg. an immobilized N6-tboc-protected adenosine with an orthogonal (photolabile) 2'-O-[(S)-1-(2-nitrophenyl)ethoxy]methyl (=(S)-npeom) group. From these building blocks, a hexameric oligoribonucleotide was prepd. by automated synthesis under std. conditions. After the detachment from the solid support, the resulting fully protected sequence was amino-acylated with L-phenylalanine derivs. carrying photolabile N-protecting groups. Upon removal of the fluoride-labile sugar- and nucleobase-protecting groups, the still stabilized, partially with the photolabile group protected precursors of an amino-acylated RNA sequence were obtained. Photolysis under mild conditions resulted in the efficient formation of the 3'(2')-O-amino-acylated RNA sequence. Addnl., we carried out model investigations concerning the stability of ester bonds of amino-acylated ribonucleotide derivs. under acidic conditions and established conditions for the purifn. and handling of 3'(2')-O-amino-acylated RNA sequences and their stabilized precursors. [on SciFinder (R)]