Amination of nucleic acid bases-A basic study on the reaction mechanism of aminating carcinogens

芳基氮离子是遗传毒性芳基羟胺的活性中间体，被认为可以修饰细胞DNA。然而，其反应机理尚不清楚。本研究是为了对核酸碱基的胺化反应有一个基本的了解。以羟胺-邻磺酸（HAOS）和2,4 -二硝基苯氧胺（DNPA）作为活化基因毒性芳基羟胺的模型。1)鸟苷（GUO）和脱氧鸟苷（dG）与HAOS或DNPA的胺化反应根据反应条件的不同得到不同的产物。在DMF中与DNPA胺化得到7-氨基-郭，它很容易转化为8,5 '- o-环郭和8-羟基郭。dG在相同的反应条件下只得到去糖基化的7-氨基鸟嘌呤。在pH高于9的条件下，HAOS对Guo和dG的胺化反应得到相应的1-氨基衍生物，而在pH为2-4的酸性介质中，主要产物分别是8-氨基-Guo和7-氨基- g。8-氨基-郭的形成机制逐渐明晰；7-NH_2-Guo 7-NH_2-8-NHOH-Guo 8- nnon - guo 8-NH_2-Guo2)虽然已知环氮甲基化鸟嘌呤和羟基化鸟嘌呤的位置异构体，但环氮胺化鸟嘌呤尚未报道。然后，我们挑战了所有n -氨基鸟嘌呤异构体的合成。以dG和O^6-甲基鸟嘌呤为底物，DNPA和HAOS为试剂，成功合成了1-氨基、3-氨基、7-氨基和9-氨基鸟嘌呤。此外，还合成了1,7 -二氨基鸟胺和3,7 -二氨基鸟胺。

Arylnitrenium ion, a reactive intermediate of genotoxic arylhydroxylamine, is considered to modify cellular DNA. However, its reaction mechanism is not clear. This study was carried out in order to obtain a basic knowledge of amination reaction of nucleic acid bases. Hydroxylamine-O-sulfonic acid (HAOS) and 2, 4-dinitrophenoxyamine (DNPA) were used as models of activated genotoxic arylhydroxylamines.1) Aminations of guanosine (GUO) and deoxyguanosine (dG) with HAOS or DNPA gave various products depending on the reaction condition. Amination of Guo with DNPA in DMF gave 7-amino-Guo, which was readily converted to 8, 5'-O-cyclo-Guo and 8-hydroxy-Guo. dG gave only deglycosylated 7-amino-guanine under the same reaction condition. Amination of Guo and dG with HAOS at above pH 9 gave the corresponding 1-amino derivatives, whereas those in acidic media at pH 2-4 gave 8-amino-Guo and 7-amino-G as the main products, respectively. The mechanism of 8-amino-Guo formation became apparent; 7-NH_2-Guo 7-NH_2-8-NHOH-Guo 8-NHON-Guo 8-NH_2-Guo. 2) Although positional isomers of ring-nitrogen methylated guanines and hydroxylated guanines are known, ring-nitrogen aminated guanines have not been reported. Then, we challenged to the synthesis of all N-aminoguanine isomers. Using dG and O^6-methylguanine (as substrates) and DNPA and HAOS (as reagents), we succeeded in the syntheses of 1-amino-, 3-amino-, 7-amino-, and 9-aminoguanines. Further, diaminoguanines, 1, 7-diamino- and 3, 7- diaminoguanines, were also synthesized.