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 N,N-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 N,N-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.
Ito et al. (Wed,) studied this question.