Oligodeoxynucleotides containing α-l-ribo configured LNA-type C-aryl nucleotides

Abstract

Synthesis of 2′-O,4′-C-methylene-α-L-ribofuranosyl derivatives containing phenyl and 1-pyrenyl aglycons, i.e., novel α-L-ribo configured LNA-type C-aryl nucleosides, has been accomplished. Key synthetic steps included stereoselective Grignard reactions on tetrahydrofuran aldehyde 12, configurational inversion of the resulting alcohol 13 into alcohol 15, and concomitant Mitsonobu cyclization furnishing the desired bicyclic furanosyl skeleton with a locked conformation. The phosphoramidite derivatives 19a and 19b were used for automated synthesis of 9-mer DNA and α-L-LNA oligonucleotides containing the α-L-LNA-type C-aryl monomers ^αLPh^L and ^αLPy^L containing a phenyl and pyrenyl aglycon, respectively. Thermal denaturation studies showed universal base pairing behavior for the pyrenyl monomer ^αLPy^L when incorporated into a DNA or an α-L-LNA oligonucleotide.