Conception and Synthesis of Oxabicyclic Nucleoside Phosphonates as Internucleotidic Phosphate Surrogates in Antisense Oligonucleotide Constructs

The stereocontrolled synthesis of a novel oxabicyclic nucleoside phosphonate comprising a perhydrofuropyran core unit was achieved. It was incorporated in an oligonucleotide sequence as a 5'-3' phosphonate phosphate insert, and the stability properties of the resulting duplex were measured. The oxabicyclic nucleoside framework was designed so as to restrict rotation around angles gamma, delta, and epsilon of a natural nucleoside.