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

作　　者：赵宝娟[1,2] 于文全[3] 常俊标[3] 李二通 丁群山 李凤娟[2] 陈光英[1] 王娜[4] 

机构地区：[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

出　　处：《高等学校化学学报》2014年第1期58-62,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21172202);海南省自然科学基金(批准号:212015)资助~~

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.Synthesis of conformationally restricted nucleosides and oligonucleotides has received much atten- tion in recent years. Moreover, it has been demonstrated that most nucleosides with fluorine in the sugar moie- ty 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＇-posi- tion 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.

关 键 词：氟原子 乙炔基 并环核苷 尿苷 

分 类 号：O626.41[理学—有机化学] O629.113[理学—化学]