有机化学 ›› 2016, Vol. 36 ›› Issue (5): 1111-1117.DOI: 10.6023/cjoc201511040 上一篇    下一篇

研究简报

(-)-牛蒡苷元及其对映异构体的不对称合成新方法

吴平, 徐凯, 付莹, 康廷国, 窦德强, 翟延君   

  1. 辽宁中医药大学药学院 大连 116600
  • 收稿日期:2015-11-19 修回日期:2015-12-21 出版日期:2016-05-25 发布日期:2016-01-15
  • 通讯作者: 翟延君 E-mail:wupingtcm@163.com
  • 基金资助:

    国家自然科学基金(No.30873437)和国家教育部博士点基金(No.20112133110001)资助项目.

A New Method for Asymmetric Synthesis of (-)-Arctigenin and Its Enantiomer

Wu Ping, Xu Kai, Fu Ying, Kang Tingguo, Dou Deqiang, Zhai Yanjun   

  1. School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600
  • Received:2015-11-19 Revised:2015-12-21 Online:2016-05-25 Published:2016-01-15
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 30873437) and the Ph.D. Program Foundation of the Ministry of Education of China (No. 20112133110001).

(-)-牛蒡苷元属于二苄基丁内酯型木脂素,是中药牛蒡子的主要活性成分.为了研究牛蒡苷元的构效关系,报道了(-)-牛蒡苷元及其对映异构体的不对称合成新方法.以苯丙酸衍生物为起始原料,首先利用噁唑烷酮类手性辅基构建丁内酯β位的手性中心,R构型和S构型β-苄基丁内酯的ee值分别为98%和96%.再利用空间位阻效应在α位构建第二个手性中心,最后脱除保护基得到目标产物.经6步反应,分别以58%、55%的总收率和97%、96%的ee值得到(-)-牛蒡苷元和(+)-牛蒡苷元.为接下来拟进行的结构优化奠定了技术基础.

关键词: 牛蒡苷元, 噁唑烷酮, Evans, 木脂素, 丁内酯, 不对称合成

(-)-Arctigenin, the main active ingredient of traditional chinese medicine (TCM) arctii fructus, belongs to dibenzyl butyrolactone lignans. In order to study the structure-activity relationship of arctigenin, a new method for asymmetric synthesis of (-)-arctigenin and its enantiomer was developed. Phenylpropanoic acid derivate was used as starting material and the chiral center of beta butyrolactone was constructed by using oxazolidinone chiral auxiliary. The eesof R and S configurations are 98% and 96%, respectively. Then the second chiral center in the alpha position was constructed benefitting from the steric effect. After removal of protecting group, the target compounds were obtained in 58 % and 55% overall yield of (-)-arcti-genin and (+)-arctigenin with 97% and 96% ee,respectively. This work paved the way for further structural optimization of arctigenin.

Key words: arctigenin, oxazolidinone, Evans, lignan, butyrolactone, asymmetric synthesis