异鸟苷掺入的富鸟嘌呤寡核苷酸的合成  

Synthesis of iso-guanosine incorporated G-rich oligonucleotide

作　　者：王延龄[1] 潘鹤龄[1] 杨振军[1] 张亮仁[1] 张礼和[1] 

机构地区：[1]北京大学药学院天然药物及仿生药物国家重点实验室,北京100083

出　　处：《中国药物化学杂志》2004年第4期225-228,235,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金 (2 0 132 0 30 );生命有机磷及化学生物学教育部重点实验室资助项目

摘　　要：目的改进异鸟苷单体的合成路线 ,合成异鸟苷掺入的富鸟嘌呤的寡核苷酸。方法以 6 O 苄基鸟嘌呤为原料 ,经环氧开环、催化氢化、水解还原制备异鸟苷 ,经多步反应后得到异鸟苷亚磷酰化产物 ,采用固相合成方法合成异鸟苷掺入的富含鸟嘌呤的寡核苷酸。结果与结论经环氧开环能够区域选择性地得到N9取代的单一产物 ,收率提高到 4 0 % ,并成功地合成了异鸟苷掺入的富含嘌呤十六聚寡核苷酸。本合成路线具有区域选择性强、路线简单、易操作、收率高等优点。Aim To improve the synthesis of isoguanosine monomer and to synthesize isoguanosine incorporated G-rich oligonucleotide.Methods Starting from 6- O -benzylguanine which reacted with epoxide 1,then was hydrolyzed and reduced,the isoguanosine was achieved.The phosphoroimidated isoguanosine was then given via several steps and solid-phase synthesis strategy was used for the synthesis of G-rich oligonucleotide.Results N9 subsititued isoguanosine was obtained regioselectively by the ring open reaction,and the yield was improved to 40%.The isoguanosine incorporated 16-mer G-rich oligonucleotide was successfully synthesized.

关 键 词：药物化学 制备 化学合成 寡核苷酸 异鸟苷 区域选择性 

分 类 号：R914[医药卫生—药物化学]