Synthesis of Methoxyethyl Nucleoside Dimer Phosphoramidites

Abstract

Four types of methoxyethyl (MOE) nucleoside phosphoramidites, which are categorized as second‐generation building blocks of antisense oligonucleotide drugs, were synthesized. Also, three types of MOE nucleoside dimer phosphoramidites were synthesized to increase the efficiency and oligomer purity in solid phase synthesis. The block‐like dimer phosphoramidites can prevent or minimize the formation of the (N‐1) mer impurity, thereby affording the fabrication of pure oligonucleotides and reducing the synthesis time by performing coupling reactions in the order of 2 + 2 + 2.