无金属脱氧反应合成抗白血病药物克拉屈滨

Efficient Synthesis of Cladribine via Metal-free Deoxygenation

报道了无金属催化脱氧反应合成标题化合物的新方法。以2-氯-3',5'-二-O-乙酰基腺苷为原料、乙腈为溶剂,2'-羟基和苯氧基硫代酰氯反应,继而以(Bu4N)2S2O8和HCO2Na为非金属脱氧试剂,代替文献报道的Bu3Sn H/AIBN体系,以DMF为溶剂,80℃反应4 h,以82%收率得到脱氧中间体。脱氧中间体在Na2CO3/CH3OH体系中脱除乙酰基。经3步反应以66.3%总收率得到克拉屈滨。该方法高效、简便,不用柱层析,易于操作,为克拉屈滨的制备提供了有效途径。

The synthesis of anti-leukemia drug Cladribine via the metal-free deoxygenation was developed.In acetonitril,2＇-hydroxyl group of 2-chloro-3＇,5＇-di-O-acetyladenosine was esterificated with phenyl thioxochloroformate.The esterificated nucleoside was deoxygenated at 80 ℃ for 4 h using（Bu4N）2S2O8and HCO2 Na instead of Bu3 Sn H/AIBN as deoxygenation system,and cladribine could be obtained in 66.3% total yield after the de-acetylation in Na2CO3/CH3 OH system.The intermediates and product could be purified by simple work-up process and chromatography was avoided,which made this route more attractive for industrial applications.