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Novel Fluoride‐Labile Nucleobase‐Protecting Groups for the Synthesis of 3′(2′)‐ O ‐Aminoacylated RNA Sequences
Author(s) -
Stutz Alfred,
Höbartner Claudia,
Pitsch Stefan
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000906)83:9<2477::aid-hlca2477>3.0.co;2-9
Subject(s) - chemistry , nucleobase , rna , protecting group , fluoride , combinatorial chemistry , stereochemistry , dna , biochemistry , organic chemistry , gene , alkyl , inorganic chemistry
With the aim to develop a general approach to a total synthesis of aminoacylated t‐RNAs and analogues, we describe the synthesis of stabilized, aminoacylated RNA fragments, which, upon ligation, could lead to aminoacylated 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 prepared ( Schemes 4 and 5 ), as well as a solid support containing an immobilized N 6 ‐tboc‐protected adenosine with an orthogonal (photolabile) 2′‐ O ‐[( S )‐1‐(2‐nitrophenyl)ethoxy]methyl (=( S )‐npeom) group ( Scheme 6 ). From these building blocks, a hexameric oligoribonucleotide was prepared by automated synthesis under standard conditions ( Scheme 7 ). After the detachment from the solid support, the resulting fully protected sequence 34 was aminoacylated with L ‐phenylalanine derivatives carrying photolabile N ‐protecting groups (→ 42 and 43 ; Scheme 9 ). Upon removal of the fluoride‐labile sugar‐ and nucleobase‐protecting groups, the still stabilized, partially with the photolabile group protected precursors 44 and 45 , respectively, of an aminoacylated RNA sequence were obtained ( Scheme 9 and Fig. 3 ). Photolysis of 45 under mild conditions resulted in the efficient formation of the 3′(2′)‐ O ‐aminoacylated RNA sequence 46 ( Fig. 4 ). Additionally, we carried out model investigations concerning the stability of ester bonds of aminoacylated ribonucleotide derivatives under acidic conditions ( Table ) and established conditions for the purification and handling of 3′(2′)‐ O ‐aminoacylated RNA sequences and their stabilized precursors.