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有机化学
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有机化学 ›› 2006, Vol. 26 ›› Issue (04): 546-550. 上一篇    下一篇

研究简报

叶酸拮抗剂Alimta的合成

郭志雄1，王荷芳1，辛春伟1，陈立功*,2   

  1. (1天津大学药物与科学技术学院 天津 300072)
    (2天津大学化工学院 天津 300072)
  • 收稿日期:2005-03-14 修回日期:2005-10-27 发布日期:2006-03-31
  • 通讯作者: 陈立功

Synthesis of Antifolate Alimta

GUO Zhi-Xiong1,WANG He-Fang1,XIN Chun-Wei1,CHEN Li-Gong*,2   

  1. (1 School of Pharmaceuticals and Biotechnology, Tianjin University, Tianjin 300072)
    (2 School of Chemical Engineering, Tianjin University, Tianjin 300072)
  • Received:2005-03-14 Revised:2005-10-27 Published:2006-03-31
  • Contact: CHEN Li-Gong

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1936

被引次数

22

吡咯并[2,3-d]嘧啶类叶酸拮抗剂Alimta (1)是一种多靶向的抗癌药物, 本工作建立了新的方法全合成该药物. 通过Friedel-Crafts反应、黄鸣龙反应制备了4-(4-乙氧基-4-氧正丁基)苯甲酸乙酯(5), 收率为36.6%. 然后采用KBH4/LiBr对5选择性还原, 再经氧化、成环等反应最终合成该药. 总收率4.8%.

关键词: 吡咯并[2,3-d]嘧啶, 黄鸣龙反应, 叶酸拮抗剂, Alimta, Friedel-Crafts反应

Antifolate alimta (1) derived from pyrrolo[2,3-d]pyrimidine is a multitargeted antitumor agent and a novel synthetic route to it was established. Ethyl 4-(4-ethoxy-4-oxobutyl)benzoate (5) was prepared via Friedel-Crafts acylation and Huang reduction in 36.6% yield, then alimta was synthesized through selective reduction with KBH4/LiBr, oxidation, ring-closing and etc. in overall yield of 4.8%.

Key words: antifolate, Huang reduction., alimta, Friedel-Crafts, pyrrolo[2,3-d]pyrimidine