以肌苷为原料的2,6-二氯嘌呤核苷的合成

Efficient Synthesis of 2,6-Dichloropurine Riboside from Cheap Inosine

摘要:

以廉价的肌苷为原料，经过糖基的乙酰化和嘌呤碱基6位羰基的氯代，得到2′,3′,5′-三-O-乙酰基-6-氯嘌呤核苷，然后以二氯甲烷为溶剂，在三氟乙酸酐和四丁基硝酸铵的作用下，在嘌呤2位引入硝基。最后在HCl/EtOH溶液中，完成脱除乙酰基和硝基氯代两步反应，得到2,6-二氯嘌呤核苷，纯度98%（HPLC），总收率63%。考察了硝基来源、氯原子来源和反应规模对收率的影响，且反应规模扩大到200 g规模时，收率无明显下降。

Abstract:

Non-costly and readily available inosine was transformed into 2′,3′,5′-tri-O-acetyl-6-chloropurineside via acetylation of sugar and chlorination of C6 carbonyl group. Then the nitro group was introduced into C2 of 2′,3′,5′-tri-O-acetyl-6-chloropurineside in CH2Cl2 with n-Bu4NNO3 and trifluoroacetic anhydride. The final product 2,6-dichloropurine riboside was synthesized in 63% total yield in HCl/EtOH solution which de-protected the acetyl groups and chlorinating the nitro group in one pot and two steps. The effects of nitro precursor, chloro precursor and reaction scales on the yields were investigated. The yield was maintained even on the 200 g scale.