Ethano <i>N,N</i> -Dicyclohexylphosphoramidite: A Capping Reagent for Solid-Phase Oligonucleotide Synthesis

In solid-phase oligonucleotide (ON) synthesis, a capping step is beneficial for obtaining a pure full-length ON. Acetic anhydride (Ac₂O) is widely used as a conventional capping reagent. However, several problems associated with acetyl capping have been reported. In this study, we developed a novel phosphoramidite-type capping reagent, ethano <i>N</i>,<i>N</i>-dicyclohexylphosphoramidite (EDCP), which was obtained as an easy-to-handle crystalline solid. EDCP, with a sterically accessible phosphorus atom, exhibited a higher capping ability than Ac₂O and diethyl <i>N</i>,<i>N</i>-diisopropylphosphoramidite, which was previously reported as a phosphoramidite-type capping reagent. Furthermore, capping-derived byproducts were not detected during solid-phase ON synthesis using EDCP. These results indicate that EDCP is a useful capping reagent that can serve as an alternative to Ac₂O and has potential applications in ON synthesis.