Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
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DOI：
10.1016/j.tet.2010.03.118
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发表时间：
2010-06-19
期刊：
影响因子：
2.1
通讯作者：
Gunning, Patrick T.
中科院分区：
文献类型：
--
作者：
Fletcher, Steven;Shahani, Vijay M.;Gunning, Patrick T.
鸟嘌呤由于其多官能性质和差的溶解性而给合成化学家带来了几个问题。在过去的几十年中，合成鸟嘌呤已经发现作为抗癌剂和抗病毒剂的应用。再加上对设计师PNA和G-四联体的日益增长的兴趣，简单而有效的合成新鸟嘌呤的路线将是显着的好处。我们在此报道，在简单的保护和/或活化步骤后，鸟嘌呤前体2-氨基-6-氯嘌呤被赋予用于Mitsunobu化学的优异底物，在随后的水解脱氯和适当的脱保护步骤后，以优异的产率（>= 80%）提供所需的N9-单-、N2-单-或N2，N9-二取代的鸟嘌呤。重要的是，我们证明了N9-官能化以非常好的N9/N7区域选择性和立体化学的完全反转进行。(C)2010爱思唯尔有限公司版权所有。
Guanine poses several problems to the synthetic chemist owing to its polyfunctional nature and poor solubility. Over the past few decades, synthetic guanines have found applications as anti-cancer and anti-viral agents. Coupled with the ever-growing interest in designer PNAs and G-quartets, simple and efficient synthetic routes to novel guanines would be of significant benefit. We herein report that, upon simple protection and/or activation step(s), the guanine precursor 2-amino-6-chloropurine is rendered an excellent substrate for Mitsunobu chemistry, furnishing, after subsequent hydrolytic dechlorination and appropriate deprotection step(s), the desired N9-mono-, N2-mono- or N2,N9-di-substituted guanines in excellent yields (>= 80%). Importantly, we demonstrate that N9-functionalization proceeds with very good N9/N7 regioselectivity and with complete inversion of stereochemistry. (C) 2010 Elsevier Ltd. All rights reserved.