军事医学2017，Vol.41Issue(8)：662-666,5.DOI:10.7644/j.issn.1674-9960.2017.08.009
磷酰胺吗啉代寡核苷酸关键中间产物的合成方法探索与工艺优化
Exploration and optimization of processes for key intermediates of phosphorodiamidate morpholino oligonucleotides
摘要
Abstract
Objective To explore and optimize the processes for synthesis of key intermediates of phosphorodiamidate morpholino oligonucleotides-7'-hydroxy-N-trityl morpholino nucleoside monomer in order to contribute to the research of phosphorodiamidate morpholino oligonucleotides antisense nucleotides.Methods With N-benzoylcytidine,guanosine and 5-methyluridine as starting materials,the ribose was modified to morpholino and the key chemical groups were protected to obtain 7'-hydroxy-N-trityl morpholino nucleoside monomer.Results Compounds N4-benzoyl-7'-hydroxy-N-trityl morpholinocytidine,N2-benzoyl-7'-hydroxy-N-trityl morpholinoguanosine and 7'-hydroxy-N-trityl morpholinothymidine were synthesized.The synthetic processes were optimized as well.The structures of all the intermediates and title compounds were characterized.Conclusion The synthetic processes of 7'-hydroxy-N-trityl morpholino nucleoside monomers have been optimized,which can be employed to prepare title compounds on a large scale.关键词
磷酰胺吗啉代寡核苷酸/吗啉核苷单体/7'-羟基-N-三苯甲基吗啉代核苷/工艺优化Key words
phosphorodiamidate morpholino oligonucleotide/morpholino nucleoside monomer/7'-hydroxy-N-trityl morpholino nucleoside/process optimization分类
医药卫生引用本文复制引用
陈晓睿,郭永建,宋亚彬,张东娜,徐力昆,王保刚,窦媛媛,王洪权..磷酰胺吗啉代寡核苷酸关键中间产物的合成方法探索与工艺优化[J].军事医学,2017,41(8):662-666,5.基金项目
国家科技重大专项资助项目(2015ZX09102022) （2015ZX09102022）
