氯法拉滨的合成工艺改进

Improved Synthesis of Clofarabine

目的合成标题化合物,并进行工艺改进。方法以1-乙酰基-2,3,5三-O-苯甲酰基-β-D-呋喃核糖为起始原料,制得1-氯-2-脱氧-2-氟-3,5-二-O-苯甲酰基-α-D-阿拉伯糖(化合物6)。化合物6与2-氯腺嘌呤在四氯化锡作用下发生缩合反应生成氯法拉滨。结果总收率为8.4%,目标化合物的结构经IR、1H-NMR、MS等方法确证。结论该合成工艺具有原料易得,操作简便,易于工业化生产等特点。

OBJECTIVE To synthesize the title compound and improve the process. METHODS 3,5-di-O-benzoyl-2-deoxy-2- fluoro-α-D-arabinofuranosyl chloride （ compound 6） was synthesizes from 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose. clofarabine was obtained by the reaction of the compound 6 and 2-chloroadenine in the presence of SnC14. RESULTS The total yield was up to 8.4%. The target compound was identified by IR, ^1H-NMR and MS. CONCLUSION The improved process is simple and easy for a scale production.