Oligodeoxynucleotides containing alpha-L-ribo configured LNA-type C-aryl nucleotides

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