The application discloses a synthesis method of phosphorodiamidate
morpholino oligonucleotide, belongs to the technical field of
solid-
phase synthesis of phosphorodiamidate
morpholino oligonucleotide, and specifically relates to the following steps: adding 9-fluorenylmethyloxycarbonyl-
piperazine-
succinic acid into
Wang resin to mix and react to synthesize 9-fluorenylmethyloxycarbonyl-
piperazine-
succinic acid-
Wang resin, then adding
phosphoramidite monomers to perform
coupling reaction after deprotection treatment, performing cap treatment after the
coupling is completed, then repeatedly performing deprotection treatment,
coupling reaction and cap treatment until the coupling of all
phosphoramidite monomers is completed, then removing the
protecting group of the last
phosphoramidite monomer, and then performing cleavage treatment and deprotection treatment of a base
protecting group to obtain a phosphorodiamidate
morpholino oligonucleotide (PMO) reaction solution. The application provides a synthesis method of phosphorodiamidate morpholino oligonucleotide with high
coupling efficiency, low
impurity level, high yield and high purity.