| abstract |
The invention discloses a pharmaceutical nucleic acid synthesis process. The invention temporarily protects unwanted groups as much as possible during the synthesis process, and after one round of coupling reaction, the protective groups on the groups in the previous round are It is selectively removed to form a specific phosphodiester bond, thereby reducing side reactions as much as possible, improving the yield of the target product, and reducing the difficulty of purification. In the present invention, the synthesis column can be simply modified, so that the synthesis column is not transferred during the aminolysis process, and the online aminolysis can elute the oligonucleic acid product loaded on the surface of the solid-phase load in the synthesis column. The eluate of the oligonucleic acid product is collected and subjected to the subsequent purification process. Since the synthesis column does not need to be offline in the whole process, on the one hand, the difficulty and complexity of the work are greatly reduced, and on the other hand, the waste gas leakage during the disassembly and installation process is significantly reduced. . |