恩曲他滨顺式和反式消旋体的简便合成
A facile synthesis of cis and trans-(±)-isomer of Emtricitabine
作者：周鸣强;沈怡;吴贝;邓勇;
Author：
收稿日期： 年卷（期）页码：2007,(01):-46-48
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：恩曲他滨;几何异构体;顺式消旋体;反式消旋体;合成
Key words：
基金项目：
中文摘要
目的研究恩曲他滨顺式和反式消旋体的合成新方法。方法以苯甲酰氧基乙醛和2,5-二羟基-1,4-二噻烷为起始原料,在对甲苯磺酸催化下环合,得1,3-氧硫杂环戊烷半缩醛(5),用SOC l2/DMF将半缩醛羟基氯代后,与硅烷化的N4-乙酰基-5-氟胞嘧啶(7)偶合,分离顺/反异构体后,用浓氨水/甲醇脱保护,分别得恩曲他滨顺式和反式消旋体。结果目标物的化学结构经1HNMR、13CNMR、MS和元素分析确证,总收率分别为51.1%和20.9%。结论方法与文献比较,具有反应条件温和、操作简便、收率高等优点。
参考文献
[1]Adis International Ltd.Emtricitabine[J].Drugs R&D,2003,4(1):42-48.
[2]Frampton JE,Perry CM.Emtricitabine.A review of its use inthe management of HIV infection[J].Drugs,2005,65(10):1427-1448.
[3]Mansour TS,Evans CA,Jin H,et al.Stereoselective synthesisof nucleoside analogs using bicyclic intermediate[P].WO9429301,1994-12-22.(CA1995,122:188037)
[4]Belleau B,Nguyen BN.Preparation of1,3-oxathiolane nucleo-sides useful in treatment of hepatitis[P].EP 515144,1992-11-25.(CA1993,118:169533)
[5]Dionne G.Preparation and virucidal activity of 1,3-oxathiolanenucleoside analogs[P].EP 526253,1993-02-03.(CA1993,119:226345)
[6]Belleau B,Mansour T,Evans CA,et al.Preparation of substitu-ted 1,3-oxathiolane nucleoside analogs with antiviral properties[P].US 5466806,1995-11-14.(CA1996,124:202959)
[7]Liotta DC,Schinazi RF,Chio WB.The preparation of 2′-deoxy-5-fluoro-3′-thiacytidine and related compounds as anti-HIVnucleosides[P].US 5210085,1993-05-11.(CA 1994,120:54903)
[8]Efimtseva EV,Mikhailov SN,Meshkov S,et al.Dioxolane nu-cleosides and their phosphonate derivatives:synthesis and hydro-lytic stability[J].J Chem Soc Perkin Trans I,1995,(11):1409-1415.
【关闭】
