Potential Purine Antagonists. XXXIV. The Synthesis of 3-Methylguanine and a Study of the Structure and Chemical Reactivity of Certain 3-Methylpurines
Potential Purine Antagonists. XXXIV. The Synthesis of 3-Methylguanine and a Study of the Structure and Chemical Reactivity of Certain 3-Methylpurines
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潜在的嘌呤拮抗剂。
DOI：
10.1021/ja00874a034
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发表时间：
1962
期刊：
影响因子：
--
通讯作者：
R. K. Robins
中科院分区：
文献类型：
--
作者：
L. Townsend;R. K. Robins
实现了3-甲基鸟嘌呤(I)的合成。对I和一些相关的2-氨基-3-甲基-6-取代嘌呤的化学性质的研究表明，这些化合物可以写成的经典的固定双键结构不能解释观察到的亲核取代的化学反应。有证据表明，这些化合物具有高度的芳香性，咪唑环上的电子密度增加，嘧啶环上的电子密度全面下降。2-氨基-1甲基-6-嘌呤硫酮2比2-氨基-6-嘌呤硫酮(6-硫代鸟嘌呤)具有更好的抗肿瘤活性，促使我们研究了6-硫代鸟嘌呤加成N-甲基衍生物的合成。2-氨基-6-嘌呤硫酮的9-甲基3和7-甲基4衍生物已被报道通过N-甲基鸟粪与吡啶中的五硫化磷的硫化反应而制备。由于所需的3-甲基鸟嘌呤(I)以前没有报道，所以I的合成是在我们的实验室进行的。考虑到Leonard和Deyrup5的工作，3-N-取代嘌呤的研究目前引起了相当大的兴趣，他们已经证明了自然产生的生物碱--三棘碱是6-氨基-3-(y，7-二甲基烯丙基)-嘌呤。此外，最近的研究表明，牛肉血液中含有尿酸-3-核糖苷。
The synthesis of 3-methylguanine (I) has been achieved. A study of the chemical properties of I and a number of re-lated 2-amino-3-methyl-6-substituted purines has revealed that the classical, fixed double-bondtype structure which can be written for these compounds does not account for the observed chemical reactivity toward nucleophilic substitution. Evidence is presented which suggests that these compounds possess a high degree of aromaticity with an increased electron density in the imidazole ring and an over-all decrease ofelectron density in thepyrimidine ring.The superior antitumor activity of 2-amino-lmethyl-6-purinethione2 over that of 2-amino-6-purinethione (6-thioguanine) against Adenocarci-noma 755 prompted us to investigate the synthesis of additionalN-methyl derivatives of 6-thioguanine. The preparation of the 9-methyl3 and 7-methyl4 derivatives of 2-amino-6-purinethione have al-ready been reported by thiation of the correspond-ing N-methylguaniue with phosphorus pentasulfide in pyridine. Since the required 3-methyl-guanine (I) has not been reported previously, the synthesis of I was undertaken in our laboratory. The study of 3-N-substituted purines is presently of considerable interest in view of the work of Leonard and Deyrup5 who have shown that the naturally-occurring alkaloid, triacanthine, is 6-amino-3-(y, 7-dimethylallyl)-purine. Also it has been shown6 recently that uric acid-3-riboside occurs in beef blood.