Oligodeoxynucleotides Containing Alpha-L-Ribo Configured Lna-Type C-Aryl Nucleotides

Synthesis of 2'- O,4'-C-methylene-alpha-L-ribofuranosyl derivatives containing phenyl and 1-pyrenyl aglycons, i.e., novel alpha-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 alpha-L-LNA oligonucleotides containing the alpha-L-LNA- type C-aryl monomers Ph-alphaL(L) and Py-alphaL(L) containing a phenyl and pyrenyl aglycon, respectively. Thermal denaturation studies showed universal base pairing behavior for the pyrenyl monomer Py-alphaL(L) when incorporated into a DNA or an alpha-L-LNA oligonucleotide.