3-羟基哌啶N,O-缩醛的不对称烯丙基化反应及在Epiquinamide和(+)-Febrifugine合成中的应用有机化学.pdfVIP

DOI: 10.6023/cjoc201304019 研究论文 有机化学 Chinese Journal of Organic Chemistry ARTICLE 3-羟基哌啶N,O-缩醛的不对称烯丙基化反应及在Epiquinamide 和 (＋)-Febrifugine 合成中的应用 冯 涛a 司长梅a 刘如成a 范 翔b 魏邦国*,a (a 复旦大学化学系 上海 200043) (b 华东理工大学生物工程学院 上海 200237) 摘要 探索了 N,O-缩醛 7 C-2 位的不对称烯丙基化的条件, 建立了路易斯酸催化条件下高选择性烯丙基化方法(产率 73%, dr 94 ∶6). 并以此为关键反应, 合成了制备( －)-Epiquinamide (1) 的关键中间体21. 作为延续性工作, 建立了一条 由(2S,3S)和(2S,3R)-9 差向异构体混合物制备光学纯( ＋)-Febrifugine (3) 的方法. 从而开发了一条以廉价谷氨酸为原料制 备克级常山碱的可能途径. 关键词 N,O-缩醛; 烯丙基化; 谷氨酸; Epiquinamide ; (＋)-Febrifugine Asymmetric Allylation of N,O-Acetal and Application in the Synthesis of Epiquinamide and ( ＋)-Febrifugine Feng, Taoa Si, Changmeia Liu, Ruchenga Fan, Xiangb Wei, Bangguo*,a a ( Department of Chemistry, Fudan University, Shanghai 200043) b ( School of Biotechnology, East China University of Science and Technology, Shanghai 200237) Abstract Lewis acid catalyzed asymmetric allylation of N,O-acetal 7 with allyltrimethylsilane was developed for the synthe- sis of compounds 9, 10 and 16 with high disasterselectivities. A key middle compound 21 for synthesis of ( －)-epiquinamide (1) was easily prepared from allylation product 16. In continuation of our work, a convenient method for synthesis of ( ＋)-febrifugine (3) was also described from the mixture of (2S,3S) and (2S,3R)-9. Therefore, a possible approach for gram scale preparation of (＋)-febrifugi