有机化学 ›› 2013, Vol. 33 ›› Issue (11): 2261-2270.DOI: 10.6023/cjoc201306006 上一篇    下一篇

综述与进展

石杉碱甲的合成研究进展

郑书岩a, 郁春辉a, 沈征武a,b   

  1. a 上海中医药大学中药学院 上海 201203;
    b 巴塞利亚药业中国有限公司 海门 226100
  • 收稿日期:2013-06-05 修回日期:2013-07-18 发布日期:2013-07-26
  • 通讯作者: 沈征武 E-mail:jeff_shen_1999@yahoo.com

Progresses in the Total Synthesis of Huperzine A

Zheng Shuyana, Yu Chunhuia, Shen Zhengwua,b   

  1. a School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203;
    b Basilea Pharmaceutical China Ltd., Haimen 226100
  • Received:2013-06-05 Revised:2013-07-18 Published:2013-07-26

石杉碱甲是中国独创的治疗老年痴呆症的药物。由于其显著的疗效,长期以来,一直受到人们的关注和研究. 目前石杉碱甲在美国已经进入三期临床研究,而在中国也已获批上市并进入四期临床. 由于石杉碱甲在千层塔中的含量仅为万分之一左右,且千层塔的生长周期较长,所以石杉碱甲的化学合成将成为获得该药物的一种有效途径. 二十多年来,化学合成石杉碱甲从消旋化合成到手性合成,从毫克级放大到几百克级合成都体现了这一领域的长足发展. 其合成工艺和路线也在安全性、实用性方面大为改善. 系统综述了1989年到2013年间石杉碱甲化学合成的进展,以期为进一步完善石杉碱甲化学合成提供参考.

关键词: 石杉碱甲, 化学合成, 综述

Huperzine A has been widely used for the treatment of alzheimer in China, and has attracted widespread attention. It has been entered into phase 3 investigation in US and phase 4 investigation in China for the treatment of alzheimer and related disease. Due to the trace content in the herb Huperzia serrata, the chemical synthesis of huperzine A becomes the attractive option for drug supply. During the past two decades, significant progresses have been achieved for the stereoselective synthesis of (-)-huperzine A. The total synthesis of hundreds of grams of (-)-huperzine A has been achieved recently. In addition to the efficiency of the synthesis, the safety of the process was also significantly improved. The progresses of the total synthesis of huperzine A made from 1989 to 2013 are comprehensively reviewed in this paper.

Key words: huperzine A, chemical synthesis, review