Straightforward Synthesis of Purine 4′-Alkoxy-2′-deoxynucleosides: First Report of Mixed Purine–Pyrimidine 4′-Alkoxyoligodeoxynucleotides as New RNA Mimics

Purine and pyrimidine 4′-alkoxy-2′-deoxynucleosides were efficiently prepared from nucleoside 4′-5′-enol acetates in three steps by <i>N</i>-iodosuccinimide promoted alkoxylation, hydrolysis, and reduction followed by conversion to phosphoramidite monomers for the solid-phase synthesis of the oligonucleotides. Fully modified 4′-alkoxyoligodeoxynucleotides, which are characterized by a prevalent <i>N</i>-type (RNA-like) conformation, exhibited superior chemical and nuclease resistance as well as excellent hybridization properties with a strong tendency for RNA-selective hybridization, suggesting a potential application of 4′-alkoxy-oligodeoxynucleotides in antisense technologies