氯法拉滨及其α异构体的合成

Synthesis of Clofarabine and Cloferabine α-isomer

目的优化合成氯法拉滨及其α异构体的合成路线。方法以2-脱氧-2-β-氟-1,3,5-三-氧-苯甲酰基-α-D-呋喃核糖经溴化反应,再与2-氯腺嘌呤在叔丁醇钾作用下缩合后,碱性条件下脱去糖基保护基制得氯法拉滨(1)和氯法拉滨α异构体(6)。结果总收率为28%,目标化合物的结构经IR、1HNMR、13CNMR、MS等方法确证。结论该合成工艺具有操作简便、产率较高、易于工业化生产等特点。

Objective To optimize the synthetic route of cloferabine （ 1 ） and cloferabine α-isomer （ 6 ）. Methods Cloferabine and eloferabine a-isomer were prepared from 2-deoxy-2-β -fluoro-1 , 3,5-tri-O-benzoyl- α-D-fibofuranose（2） via bromination and subjected to condensation with 2-chloroadenine followed by separa- tion and deprotection. Results The overall yield was up to 28%. The target compound was identified by IR, ^1 HNMR,^ 13CNMR and MS. Conclusion The improved process is simple, easy and applicable to scale produc- tion.