抗肿瘤药物卡培他滨的合成新方法

New Method for Synthesis of Antitumor Drug Capecitabine

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.

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.