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