Exploration and optimization of processes for key intermediates of phosphorodiamidate morpholino oligonucleotides
10.7644/j.issn.1674-9960.2017.08.009
- VernacularTitle: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
- Author:
rui Xiao CHEN
1
;
jian Yong GUO
;
bin Ya SONG
;
na Dong ZHANG
;
kun LI XU
;
gang Bao WANG
;
yuan Yuan DOU
;
quan Hong WANG
Author Information
1. 军事医学科学院微生物流行病研究所,病原微生物生物安全国家重点实验室,北京100071
- Keywords:
phosphorodiamidate morpholino oligonucleotide;
morpholino nucleoside monomer;
7'-hydroxy-N-trityl morpholino nucleoside;
process optimization
- From:
Military Medical Sciences
2017;41(8):662-666
- CountryChina
- Language:Chinese
-
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.
