微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物  

Stereospecific Synthesis of ω-Amino-β-D-furanoribosyl Acetic Acid Based on Microwave Assisted Wittig-Michael Tandem Reaction

作　　者：马东来[1] 李小六[1] 郝乐[1] 张平竹[1] 陈华[1] 赵影[2] 

机构地区：[1]河北大学化学与环境科学学院,河北省化学生物学重点实验室,保定071002 [2]河北农业大学理学院,保定071001

出　　处：《高等学校化学学报》2014年第5期959-964,共6页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21172051;21372060);河北省重点基础研究项目(批准号:12966417D);河北省自然科学基金(批准号:Y2011119;ZH2011110);河北省自然科学基金石药集团医药联合基金(批准号:B2011201169;B2012201113)资助~~

摘　　要：以D-核糖为原料,在微波促进下,利用2,3-O-异丙叉基-D-核糖2与叶立德3(Ph3P CHCOOEt)的Wittig反应和Michael加成,立体专一性地合成了β-D-呋喃核糖酸酯类化合物,再经叠氮化及还原反应,得到ω-氨基-β-D-呋喃核糖酸衍生物.在微波辐射下,该Wittig-Michael串级反应的效率得到显著提高,反应时间由12 h缩短为10 min,收率达到91%.反应具有非常好的β-立体选择性,在碱性条件下处理后,α-异构体可转变成热力学稳定的β-异构体,从而得到单一的β-异构体.计算结果表明,β-异构体4b比α-异构体4a具有更高的热力学稳定性.An efficient and stereoselective method for synthesizing ω-amino-β-D-furanoribosylactic ester was established based on the microwave assisted Wittig-Michael tandem reaction of acetone protection of D-ribose （2） and Ylide 3（Ph3P CHCOOEt）, and followed by ω-azidation and reduction. The microwave assisted Wittig-Michael addition reaction was carried out effectively andβ-stereoselectively in CH3 CN at 115 ℃ with a yield up to 91% within 10 min, and theα-stereomer could easily converted to the thermodynamically more sta-ble β-stereomer during workup in basic condition. The calculation results of quantum chemistry show thatβ-isomer 4b is higher thanα-isomer 4a in thermodynamic stability. The structures of the compounds were iden-tified by spectral analyses of 1 H NMR, 13 C NMR and HRMS.

关 键 词：氨基呋喃核糖酸酯 微波促进反应 Wittig-Michael串级反应 

分 类 号：O629.11[理学—有机化学]