南昌大学学报(理科版)2024,Vol.48Issue(1) :71-76.

一种新型磷酰胺吗啉代寡鸟苷酸单体的合成及工艺优化

Synthesis and process optimization for a novel phosphorodiamidate morpholinoguanylic monomer

欧阳红霞 杨小喆 李海峰 丁永红 李亮荣
南昌大学学报(理科版)2024,Vol.48Issue(1) :71-76.

一种新型磷酰胺吗啉代寡鸟苷酸单体的合成及工艺优化

Synthesis and process optimization for a novel phosphorodiamidate morpholinoguanylic monomer

欧阳红霞 1杨小喆 2李海峰 3丁永红 2李亮荣1
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作者信息

  • 1. 南昌大学抚州医学院,江西抚州 344000;抚州市AI药物技术创新中心,江西抚州 344000
  • 2. 南昌大学抚州医学院,江西抚州 344000
  • 3. 江西省肿瘤医院核医学,江西南昌 330029
  • 折叠

摘要

发展了一种以鸟苷为原料的新型磷酰胺吗啉代寡鸟苷酸单体的合成路线.在对碱基上氨基和核糖5'位羟基进行保护的基础上,将核糖环转变为吗啉环,得到保护的吗啉代鸟苷.在吗啉环上进行三苯甲基化反应,并利用Mitsunobu反应对嘌呤6-O位进行修饰;对脱保护后的羟基进行N,N-二甲基氨基磷酰化反应,合成得到 目标产物.对Mitsunobu反应和磷酰化反应的条件进行了优化.在优化的条件下,新合成路线的总产率为14.1%.通过LC-MS、1H NMR和31P NMR等技术手段对中间产物和目标产物进行了结构表征.

Abstract

A synthesis route of a novel phosphoramide morpholinoline-oligoguanylate monomer using guanosine as raw ma-terial was developed.Based on the protection of the amino group on the base and 5'-OH in ribose,the ribose ring is converted in-to a morpholine ring to obtain the protected morpholine guanosine.A triphenylmethylation reaction was carried out on the mor-pholine ring and purine 6-O position was modified using the Mitsunobu reaction.N,N-dimethylaminophosphorylation reaction is performed on the deprotected hydroxyl group to synthesize the target product.In this study,the conditions of the Mitsunobu re-action and phosphorylation reaction were optimized.Under optimized conditions,the total yield of the new synthetic route was 14.1%.The structure of intermediate products and target products were characterized by LC-MS,1 H NMR and 31P NMR.

关键词

合成/鸟苷/吗啉代寡鸟苷酸/Mitsunobu反应/磷酰化反应

Key words

synthesis/guanosine/morpholino-oligoguanylate/mitsunobu reaction/phosphorylation reaction

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基金项目

国家自然科学基金(21863006)

江西省教育厅科学技术研究项目(GJJ208903)

抚州市科技指导项目(20220906)

出版年

2024
南昌大学学报(理科版)
南昌大学

南昌大学学报(理科版)

CSTPCD
影响因子:0.418
ISSN:1006-0464
参考文献量19
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