一种合成2-巯基腺苷的新方法

New Synthesis of 2-Thioadenosine

报道了一种合成重要的核苷药物中间体2-巯基腺苷的新方法。以2,6-二氯嘌呤和四乙酰核糖为原料,经过缩合、氨解得到2-氯腺苷,继而以DMF为溶剂,和商品化的固体Na2S在90℃反应10 h,以3步和77%的总收率得到标题化合物。考查反应溶剂、原料配比及反应规模对收率的影响。该方法避免了传统方法中需要新制Na2S的苛刻条件,原料廉价易得,且反应规模扩大至100 g时,收率没有降低。

A new method for the synthesis of 2-thioadenosine was developed. The key intermediate 2-chlroadenosine was obtained from 2,6-dichloropurine and beta-D-ribofuranose 1,2,3,5-tetraacetate via condensation and ammonolysis steps. The C2-Cl was substituted by commercially available Na2 S at 90 ℃ for 10 h in DMF,affording 2-thioadenosine in 77% total yield. The effects of solvents,substrate ratios and reaction scale on the yields were investigated. The presented method avoided the tedious reaction conditions and newly made Na2 S reported in literature. The starting substrates were all commercially available and not costly. Moreover,2-thioadenosine was afforded successfully in maintained yield even on a 100 g scale.