Synthesis of pyrene and benzo[a]pyrene adducts at the exocyclic amino groups of 2'-deoxyadenosine and 2'-deoxyguanosine by a palladium-mediated C-N bond-formation strategy.
Synthesis of pyrene and benzo[a]pyrene adducts at the exocyclic amino groups of 2'-deoxyadenosine and 2'-deoxyguanosine by a palladium-mediated C-N bond-formation strategy.
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通过钯介导的 C-N 键形成策略在 2-脱氧腺苷和 2-脱氧鸟苷的环外氨基处合成芘和苯并[a]芘加合物。
DOI：
10.1021/jo030113b
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Mah,Heduck
中科院分区：
文献类型：
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作者：
Lakshman,MaheshK;Ngassa,FelixN;Bae,Suyeal;Buchanan,DennisG;Hahn,Hoh-Gyu;Mah,Heduck
致癌碳氢化合物苯并[a]芘（BaP）的单电子氧化被认为会产生一种自由基阳离子中间体，这种物质被认为会在嘌呤核碱基的氮上引起烷基化。虽然已经分离出几种不同的核苷加合物，因为它们是由这种代谢活化模式产生的，但迄今为止，还没有选择性地全合成由任何烃与嘌呤2 '-脱氧核苷单电子氧化形成的稳定的环外氨基加合物。在本文中，我们公开了模型加合物N6-（1-芘基）-2 '-脱氧腺苷和N2-（1-芘基）-2'-脱氧鸟苷的合成，以及致癌物连接的核苷衍生物N6-（6-苯并[a]芘基）-2 '-脱氧腺苷和N2-（6-苯并[a]芘基）-2'-脱氧鸟苷通过钯介导的C-N键形成的首次合成。尝试了两种不同的偶联策略：芳基溴与适当保护的核苷的偶联和芳基胺与合适的卤代糖苷的偶联。前者的适用性有限，因为该方法只能制备N6-（1-芘基）-2 '-脱氧腺苷，而后者的适用性较广。然而，在C-6和C-2位置的胺化反应中存在值得注意的差异。在C-6位的反应导致除了所需的单芳基核苷之外，还竞争形成1：2的胺-核苷加合物。在C-2处未观察到这种二聚体形成。然而，C-2加合物显示出有趣的构象行为。
Single-electron oxidation of the carcinogenic hydrocarbon benzo[a]pyrene (BaP) is thought to result in a radical cation intermediate and this species has been proposed to cause alkylation at the nitrogens of the purine nucleobases. Although several different nucleoside adducts have been isolated as arising from this mode of metabolic activation, there are no selective, total syntheses of the stable exocyclic amino group adducts formed by the single-electron oxidation of any hydrocarbon with the purine 2‘-deoxynucleosides to date. In this paper we disclose the synthesis of the model adductsN6-(1-pyrenyl)-2‘-deoxyadenosine andN2-(1-pyrenyl)-2‘-deoxyguanosine as well as the first synthesis of the carcinogen-linked nucleoside derivativesN6-(6-benzo[a]pyrenyl)-2‘-deoxyadenosine andN2-(6-benzo[a]pyrenyl)-2‘-deoxyguanosine via a palladium-mediated C−N bond formation. Two different coupling strategies were attempted: coupling of an aryl bromide with a suitably protected nucleoside and the coupling of an arylamine with a suitable halonucleoside. The former had somewhat limited applicability in that onlyN6-(1-pyrenyl)-2‘-deoxyadenosine was prepared by this method; on the other hand, the latter was more general. However, there are noteworthy differences in the amination reactions at the C-6 and C-2 positions. Reactions at the C-6 resulted in the competing formation of a 1:2 amine−nucleoside adduct in addition to the desired monoaryl nucleoside. Such a dimer formation was not observed at the C-2. The C-2 adducts, however, displayed an interesting conformational behavior.
狗和兔血浆对碳酸酐酶的抑制作用。
DOI：
10.1152/jappl.1986.60.1.191
发表时间：
1986
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
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作者：
Hill,EP
通讯作者：
Hill,EP