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3-去氮-Neplanocin A(3-DNPA,2)是具有很强抗病毒抗肿瘤活性的碳环核苷。发展其有效的合成路线,有助于其类似物的合成及进一步的生物活性研究。由2,4-二羟基-3-硝基吡啶起始的3-去氮嘌呤合成,采用一釜反应直接构建咪唑环,避免了中间体10被氧化;同时,碱基合成中副产物11-1的发现和结构确证,提示了一条合成1-去氮嘌呤的新方法。采用微波辅助方法提高了6-氯-3-去氮嘌呤12的肼解及随后的Boc保护制备17的反应产率;而后者提高了偶联反应N9异构体的比例。全部合成工作经十步反应得到3-DNPA,总收率11.2%。
3-Deaza-Neplanocin A (3-DNPA, 2) is a carbocyclic nucleoside with strong anti-viral anti-tumor activity. The development of its effective synthetic route contributes to the synthesis of its analogues and further study of its biological activity. The synthesis of 3-deazapurine starting from 2,4-dihydroxy-3-nitropyridine, using a one-pot reaction to directly construct the imidazole ring, avoids the oxidation of intermediate 10; in the meantime, byproduct 11- 1 discovery and structural confirmation, suggesting a new method of synthesizing 1-deazapurine. The microwave assisted approach improves the hydrazinolysis of 6-chloro-3-deazapurine 12 and the subsequent reaction yield of Boc protection to prepare 17; the latter increases the proportion of the N9 isomer in the coupling reaction. 3-DNPA was obtained from all the reactions in ten steps and the total yield was 11.2%.