An efficient synthesis of enantiomeric ribonucleic acids from D-glucose

Enantiomeric oligoribonucleotides (ent-RNA) up to a sequence length of 35, consisting of the (L-configurated) nucleosides ent-adenosine, ent-guanosine, ent-cytidine, ent-uridine, and 1-(b-L-ribofuranosyl)thymine were prepd. by automated synthesis from appropriate building blocks, carrying a known photo-labile 2'-O-protecting group. A simple large-scale synthesis of 1,2,3-tri-O-benzoyl-5-O-(triisopropylsilyl)-L-ribose from L-glucose and its straightforward conversion into phosphoramidites and solid supports, resp., were elaborated. Within this project, a novel, superior strategy for the synthesis of 2'-O-{[(2-nitrobenzyl)oxy]methyl} nucleosides as key intermediates by regioselective alkylation of their 5'-O-dimethoxytritylated precursors was developed. Furthermore, an improved set-up for the final light-induced cleavage of the 2'-O-protecting groups from the oligonucleotide sequences was designed. The correct compn. of all ent-oligoribonucleotides prepd. was established by their MALDI-TOF mass spectra. The 1H NMR of a dodecameric ent-RNA sequence was in excellent agreement with the published data of its natural counterpart, synthesized by conventional methods. The known specific cleavage of a tetradecamer sequence by a 35mer ribozyme structure could be reproduced by ent-oligoribonucleotides, synthesized by the presented methods. [on SciFinder (R)]