高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (08): 1733.doi: 10.3969/j.issn.0251-0790.2012.08.019

• 有机化学 • 上一篇    下一篇

抗肿瘤药物卡培他滨的合成新方法

赵明礼, 赵玉涛, 张召, 高洁, 屈文, 徐锦梅, 刘宏民   

  1. 郑州大学药学院, 新药研究开发中心, 郑州 450001
  • 收稿日期:2011-11-07 出版日期:2012-08-10 发布日期:2012-08-10
  • 通讯作者: 刘宏民, 男, 博士, 教授, 博士生导师, 主要从事药物分子的设计合成研究. E-mail: liuhm@zzu.edu.cn E-mail:liuhm@zzu.edu.cn
  • 基金资助:

    国家自然科学基金(批准号: 81172937)资助.

New Method for Synthesis of Antitumor Drug Capecitabine

ZHAO Ming-Li, ZHAO Yu-Tao, ZHANG Zhao, GAO Jie, QU Wen, XU Jin-Mei, LIU Hong-Min   

  1. New Drug Research and Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
  • Received:2011-11-07 Online:2012-08-10 Published:2012-08-10

摘要: 研究了抗肿瘤药物卡培他滨的合成新方法. 该方法以廉价的D-木糖为原料制得重要中间体1,2,3-三-O-乙酰基-5-脱氧-D-呋喃核糖(5), 化合物5再与5-F胞嘧啶进行Vorbrueggen反应, 然后经酰胺化, 脱除乙酰基得到卡培他滨, 合成总收率为29.8%. 该方法的关键步骤是化合物3的3-OH构型翻转和5-对甲苯磺酰氧基基团(5-OTs)的还原脱除。结果表明, 该方法原料廉价易得、 反应条件温和、 操作简单、 收率良好且产物易于分离纯化, 适合大规模制备.

关键词: 卡培他滨, D-木糖, 抗肿瘤药物

Abstract: Capecitabine, a prodrug of antitumor agent 5-fiuorouracil, is currently to be approved for use as therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. This drug can be orally home-administered, which offers patients more freedom and reduces the costs of therapy. Here a novel method for synthesis of capecitabine was reported. The key intermediate, 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose, was prepared from D-xylose. Capecitabine was synthesized through Vorbrueggen reaction, amidation and hydrolization of acetyl group with 29.8% overall yield. The key steps, the configuration change of the 3-hydroxy group through oxidation and reduction and the deoxygenation of sulfonyloxy activated sugar hydroxyl groups by reductive displacement employing NaBH4, were optimized. This method has the advantages of easily available and cheap starting materials, simply conducted procedures, relatively high yield and easy purification. So this new method is more suitable for scale-up production.

Key words: Capecitabine, D-Xylose, Antitumor agent

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