抗白血病药物克拉屈滨的合成  

Synthesis of Anti-leukemia Drug Cladribine

作　　者：夏然[1] 孙莉萍[2] 渠桂荣[3] 陈磊山[1] 

机构地区：[1]新乡学院化学化工学院,河南新乡453003 [2]新乡学院生命科学与技术学院,河南新乡453003 [3]河南师范大学化学化工学院,河南新乡453007

出　　处：《应用化学》2016年第11期1274-1278,共5页Chinese Journal of Applied Chemistry

基　　金：国家自然科学基金(21172059);河南省高等学校重点科研项目(16A150042)资助项目~~

摘　　要：报道了抗白血病药物克拉屈滨的合成新方法:在NaH作用下,廉价易得的6-氯嘌呤高选择性地在β位和1-氯-2-脱氧-3,5-二-O-对氯苯甲酰基-D-核糖缩合;β-缩合物的2位在三氟乙酸酐和四丁基硝酸铵作用下引入硝基;在NH_4Cl/EtOH作用下,2-硝基转化为2-氯;最后在饱和NH_3/CH_3OH溶液中完成保护基脱除和6-氯氨解两步反应,以4步共43.5%的总收率得到抗白血病药物克拉屈滨。该方法完全避免了α异构体的生成,原料廉价易得,分离纯化不需柱层析,且反应扩大到100 g规模时,收率无下降,具有较好的应用前景。Cladribine, an anti-leukemia drug, was synthesized in 43.5% total yield by 4 steps. Readily available 6-chloropurine was glycosylated with 1-chloro-3,5-di-O-p-benzoyl-D-ribose with good selectivity for fl anomer in the presence of Nail. The C2-H of β-glycosylated product was converted into C2-NO2 using 2,2,2- trifluoroacetic anhydride and tetrabutylammonium nitrate, followed by the transformation of C2-NO2 into C2-Cl in NH4Cl/EtOH solution. The deprotection step and ammonolysis of C6-Cl were accomplished in NH3/CH3OH. The separation of α-anomer, expensive starting materials and chromatography are not required. Moreover, cladribine could be produced on a 100 gram scale with maintained yield, indicating good potential in industrial applications.

关 键 词：氯嘌呤 克拉屈滨 硝化反应 规模合成 

分 类 号：O622.1[理学—有机化学]