Disclosed are processes for preparing oligonucleotides. The process comprises: (a) converting a compound of Formula X-1 into a compound of Formula X-2: where R10 is a residue of an oligonucleotide (e.g., a phosphorodiamidate morpholino oligomer); R11 is an amine protecting group; wherein the compound of Formula X-1 is not bound to a solid support; and; (b) optionally removing protecting groups in the compound of Formula X-2 to obtain the oligonucleotide. The synthetic processes described herein are advantageous in many aspects, including but not limited to improved yields and purities of target phosphorodiamidate morpholino oligomers with reduced 4-nitrostyrene adduct impurities. (X-1), (X-2)
公开了制备寡
核苷酸的过程。该过程包括:(a)将式X-1的化合物转化为式X-2的化合物:其中R10是寡
核苷酸的残基(例如,
磷酸二
酰胺吗啉寡聚体);R11是胺保护基;其中式X-1的化合物未结合到固体支持上;以及;(b)可选地去除式X-2的化合物中的保护基,以获得寡
核苷酸。本文所描述的合成过程在许多方面具有优势,包括但不限于提高目标
磷酸二
酰胺吗啉寡聚体的产率和纯度,并减少
4-硝基苯乙烯加合物
杂质。(X-1),(X-2)