索非布韦核苷中间体异构体的合成  

Synthesis of the Intermediate Isomer of Sofosbuvir

作　　者：彭晓含 夏天 陈达 张珍明 李树安 PENG Xiao-han;XIA Tian;CHEN Da;ZHANG Zhen-ming;LI Shu-an(College of Chemical Engineering,Jiangsu Ocean University,Lianyungang 222005,China;College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]江苏海洋大学化学工程学院,江苏连云港222005 [2]江苏海洋大学药学院,江苏连云港222005

出　　处：《合成化学》2020年第9期801-805,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21606095);国家海洋公益性行业科研专项(201305007);江苏省研究生科研创新计划(KYCX18-2610)。

摘　　要：以S-甘油醛缩丙酮为原料,经Wittig反应、高锰酸钾氧化、磺酰化、氟化、水解、内酯化得索非布韦关键中间体的异构体(3R,4R,5S)-3-氟-4-羟基-5-(羟基甲基)-3-甲基四氢呋喃-2-酮,优化反应条件:n(磺酰氯)/n(化合物3)=1.6/1.0,温度为-10℃,反应2 h;氟化试剂为TEAF(四乙基氟化铵),温度为100℃,反应3 h,制得5S-核苷的总收率为14.21%,化学纯度97.5%,ee值98.4%,经1HNMR,IR和MS(ESI)表征。The key intermediates(3R,4R,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyl-dihydrofuran-2(3H)-one for the impurity isomers of Sofosbuvir was synthesized via Wittig reaction,potassium permanganate oxidation,sulfonylation,fluorination,hydrolysis,lactonization from S-glyceraldehyde acetonide as raw material.Optimized reaction conditions:n(sulfonyl chloride)/n(compound 3)=1.6/1.0,reacting at-10℃for 2 h;the fluorination reagent was tetraethylammonium fluoride and reacting at 100℃for 3 h,the total yield of 5S-nucleoside was 14.21%,the purity and ee value were 97.5%and 98.4%,respectively.The structure was characterized by 1H NMR,IR and MS(ESI).

关 键 词：索非布韦 S-甘油醛缩丙酮 5S-核苷中间体 合成 异构体 

分 类 号：TQ630[化学工程—精细化工] O625.7[理学—有机化学]