Solid‐Phase Synthesis of 2′‐O‐Methoxyethyl Oligonucleotides Using Dimeric Phosphoramidite Blocks

Abstract

This research focused on the method of using dimeric phosphoramidite blocks to synthesize oligonucleotides for development as oligonucleotide drugs. A 16‐mer oligonucleotide with the randomly selected sequence of C*C*T*C*G*C*T*C*T*C*G*C*C*C*G*C was synthesized using CC, GC, and TC dimers, a combination of monomers and dimers, or only monomers as building blocks. Using dimer blocks in this synthetic method provided a significant decrease in critical impurities that had similar properties to the main product, which was confirmed by LC‐MS and HPLC analysis.