Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives
Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives
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DOI：
10.1039/b300557g
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Sajiki, H
中科院分区：
文献类型：
--
作者：
Hirota, K;Kazaoka, K;Sajiki, H
实现了一种高效、通用的合成具有多种生物活性的2，9-二取代8-羟基腺嘌呤的方法。以氨基丙二腈和异氰酸酯为主要中间体合成了5-氨基-4-氰基-2-羟基咪唑类化合物(1)。1a与酰胺、酰亚胺、胍、尿素和硫脲缩合，得到2-位具有不同取代基的8-羟基腺嘌呤(2-6)。此外，2-氨基和2-羟基腺嘌呤(4和6)的选择性烷基化反应分别得到相应的2-烷基氨基和2-烷氧基腺嘌呤(5和7)。通过1a与苯甲酰异硫氰酸酯的类似反应和随后的S烷基化反应合成了2-烷基硫代腺嘌呤(15)。咪唑类化合物1是合成8-羟基腺嘌呤衍生物最有用的中间体。
An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-Amino-4-cyano-2-hydroxyimidazoles (1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2-6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkylthioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediates for the synthesis of 8-hydroxyadenine derivatives.