Phosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. Furthermore, phosphonium-type condensing reagents facilitated the fragment condensation of PMO, synthesizing up to 8-mer containing all four nucleobases with remarkable coupling efficacy. This is the first report on the convergent synthesis of PMOs. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.

磷酸二酰胺吗啉代寡核苷酸 (PMO) 是一种很有前途的反义寡核苷酸，但其合成具有挑战性，使其难以获得。本研究提出了一种使用H-膦酸盐方法有效合成 PMO 的方法。与目前的合成方法相比，鏻型缩合试剂的使用显着减少了偶联时间。此外，鏻型缩合试剂促进了PMO的片段缩合，合成了包含所有四种核碱基的多达8聚体，具有显着的偶联功效。这是第一篇关于 PMO 收敛合成的报告。这种方法将促进 PMO 的大规模合成，并加速其作为下一代疗法的普及和可及性。