An Efficient Synthesis of Enantiomeric Ribonucleic Acids from D ‐Glucose

Enantiomeric oligoribonucleotides (= ent ‐RNA) up to a sequence length of thirty‐five and consisting of the ( L ‐configurated) nucleosides ent ‐adenosine, ent ‐guanosine, ent ‐cytidine, ent ‐uridine, and 1‐(β‐ L ‐ribofuranosyl)thymine were prepared by automated synthesis from appropriate building blocks, carrying a known photo‐labile 2′‐ O ‐protecting group. A simple large‐scale synthesis of the new, prefunctionalized L ‐ribose derivative 5 from D ‐glucose ( Scheme 1 ) and its straightforward conversion into the five phosphoramidites 28 – 32 and five solid supports 38 – 42 , respectively, were elaborated ( Scheme 4 ). Within this project, a novel, superior strategy for the synthesis of the 2′‐ O ‐{[(2‐nitrobenzyl)oxy]methyl}‐substituted key intermediates 18 – 22 by regioselective alkylation of their 5′‐ O ‐dimethoxytritylated precursors 13 – 17 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 ( Scheme 5 and Fig. 1 ). The correct composition of all ent ‐oligoribonucleotides prepared was established by their MALDI‐TOF mass spectra. The 1 H‐NMR‐spectroscopic data 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 ( Fig. 4 ).