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2019 , Vol. 39 >Issue 11: 3237 - 3243

DOI: https://doi.org/10.6023/cjoc201904074

研究论文

通过Michael加成引发分子间的环丙烷化反应高效合成螺环嘧啶核苷

  • 郝二军 ,
  • 张庆 ,
  • 张齐英 ,
  • 渠桂荣 ,
  • 杨西宁 ,
  • 郭海明
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  • a河南师范大学化学化工学院 精细化学品绿色制造河南省协同创新中心 河南省有机功能分子与药物创新重点实验室 河南新乡 453007
    b 新乡拓新药业股份有限公司 河南新乡 453000

收稿日期: 2019-04-30

  网络出版日期: 2019-06-24

基金资助

国家自然科学基金(21602045);国家自然科学基金(U1604283);河南省博士后科学基金(2015071);高等学校学科创新引智计划(111计划);高等学校学科创新引智计划(D17007)

收起

Efficient Synthesis of Spirocyclic Nucleosides via Michael Addition-Initiated Intermolecular Cyclopropanation Reaction

  • Erjun Hao ,
  • Qing Zhang ,
  • Qiying Zhang ,
  • Guirong Qu ,
  • Xining Yang ,
  • Haiming Guo
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  • aHenan Key Laboratory of Organic Functional Molecules and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007
    b Xinxiang Tuoxin Pharmaceutical Co., Ltd., Xinxiang, Henan 453000

Received date: 2019-04-30

  Online published: 2019-06-24

Supported by

the National Natural Science Foundation of China(21602045);the National Natural Science Foundation of China(U1604283);the Henan Postdoctoral Science Foundation Funded Project(2015071);Overseas Expertise Introduction Project for Discipline Innovation(111计划);Overseas Expertise Introduction Project for Discipline Innovation(D17007)

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摘要

报道了一种简单高效的螺环核苷合成方法，以α-嘧啶取代的丙烯酸酯和α-氯代环烷酮为原料，KOtBu为碱，通过Michael加成引发的环丙烷化反应，高效合成一系列2'-螺环修饰的三元碳环嘧啶核苷.该反应底物适用范围较宽，非对映选择性较高（>20：1 dr），收率可高达85%.

关键词： 螺环核苷; 环丙烷化反应; α-氯代环烷酮; spirocyclic nucleoside; cyclopropanation reaction; α-chloro-cycloalkanone

本文引用格式

郝二军 , 张庆 , 张齐英 , 渠桂荣 , 杨西宁 , 郭海明 . 通过Michael加成引发分子间的环丙烷化反应高效合成螺环嘧啶核苷[J]. 有机化学, 2019 , 39(11) : 3237 -3243 . DOI: 10.6023/cjoc201904074

Abstract

An efficient route to synthesize 2'-spiro[2-oxocyclopentyl]cyclopropyl nucleoside analogues via KOtBu promoted Michael addition-initiated cyclopropanation reactions of α-thymine acrylates with α-chloro-cycloalkanones has been developed. A wide range of C(2')-spirocyclic modified nucleoside analogues were obtained with excellent diastereoselectivities (>20:1) and good yields (up to 85%).

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