3'-氟-2'-O,3'-C-乙烯基键联并环尿苷的合成与表征

doi:10.7503/cjcu20130395

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (1): 58.doi: 10.7503/cjcu20130395

3'-氟-2'-O,3'-C-乙烯基键联并环尿苷的合成与表征

赵宝娟^1,², 于文全³, 常俊标³(), 李二通³, 丁群山³, 李凤娟², 陈光英¹, 王娜⁴

1. 天津工业大学环境与化学工程学院制药工程系, 天津 300387
2. 海南师范大学化学与化工学院, 海南省热带药用植物化学重点实验室, 海口 571158
3. 郑州大学化学与分子工程学院, 郑州 450001
4. 湖北中烟工业有限责任公司, 武汉 430040

收稿日期:2013-04-28 出版日期:2014-01-10 发布日期:2013-12-11
作者简介:联系人简介: 常俊标, 男, 博士, 教授, 博士生导师, 主要从事药物化学研究. E-mail:changjunbiao@zzu.edu.cn
基金资助:
国家自然科学基金(批准号: 21172202)和海南省自然科学基金(批准号: 212015)资助

Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine^†

ZHAO Baojuan^1,², YU Wenquan³, CHANG Junbiao^3,^*(), LI Ertong³, DING Qunshan³, LI Fengjuan², CHEN Guangying¹, WANG Na⁴

1. School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387, China
2. Key Laboratory of Tropical Medicinal Plant Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China
3. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China
4. China Tobacco Hubei Industrial Co. Ltd., Wuhan 430040, China

Received:2013-04-28 Online:2014-01-10 Published:2013-12-11
Contact: CHANG Junbiao E-mail:changjunbiao@zzu.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(No.21172202) and the Natural Science Foundation of Hainan Province of China(No.212015)

摘要/Abstract

摘要：

设计合成了氟化并环核苷衍生物3'-氟-2'-O,3'-C-乙烯基键联的并环尿苷(1), 并通过¹H NMR, ¹³C NMR和HRMS分析表征了其结构. 同时, 对具有乙炔基及氟原子取代的重要中间体7的结构进行了分析确证, 并提出其可能的形成机理.

关键词: 氟原子, 乙炔基, 并环核苷, 尿苷

Abstract:

Synthesis of conformationally restricted nucleosides and oligonucleotides has received much attention in recent years. Moreover, it has been demonstrated that most nucleosides with fluorine in the sugar moiety possess potent antitumor and/or antiviral activities. However, to the best of our knowledge, there are few reports on conformationally restricted nucleosides with fluorinated sugar moiety. Herein, we report the design and synthesis of a novel fluorinated bicyclic nucleoside, 3'-deoxy-3'-fluoro-2'-O,3'-C-vinylene linked bicyclic uridine, via an eleven-step synthesis from D-xylose. The synthetic route involved ethynylation in the sugar ring, diethylaminosulphur trifluoride(DAST)-mediated fluorination and configuration inversion at the 3'-position to give the key intermediate 7, which then coupled with nucleobase, followed by deprotection and ring closure under basic conditions to afford the target compound 1. Its structure was characterized by ¹H NMR, ¹³C NMR and HRMS. A plausible mechanism for the formation of the key intermediate 7 was proposed. It could be rationalized by the neighbouring group participation of the 3-benzoate ester and the generation of the benzoxonium ion B. The present work provides an efficient tool for the construction of biologically interesting fluorinated bicyclic nucleosides and their analogues.

Key words: Fluoro, Ethynyl group, Bicyclic nucleoside, Uridine

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赵宝娟, 于文全, 常俊标, 李二通, 丁群山, 李凤娟, 陈光英, 王娜. 3'-氟-2'-O,3'-C-乙烯基键联并环尿苷的合成与表征. 高等学校化学学报, 2014, 35(1): 58.

ZHAO Baojuan, YU Wenquan, CHANG Junbiao, LI Ertong, DING Qunshan, LI Fengjuan, CHEN Guangying, WANG Na. Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine^†. Chem. J. Chinese Universities, 2014, 35(1): 58.

图/表 3

参考文献 21

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3'-氟-2'-O,3'-C-乙烯基键联并环尿苷的合成与表征

Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine^†

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3'-氟-2'-O,3'-C-乙烯基键联并环尿苷的合成与表征

Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine†

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Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine^†