Niles J C, Wishnok J S, Tannenbaum S R
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Chem Res Toxicol. 2000 May;13(5):390-6. doi: 10.1021/tx0000318.
A novel nitration product, formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine, has been characterized using a combination of UV/vis, CD, and NMR spectroscopy and mass spectrometry. This compound has been identified as N-nitro-N'-[1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-2, 4-dioxoimidazolidin-5-ylidene]guanidine (IV). Upon base hydrolysis, IV releases nitroguanidine (IVa) and an intermediate, 1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-iminoimidazolidine -2, 4-dione (IVb). This intermediate is ultimately hydrolyzed to the stable 3-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)oxaluric acid (IVc). IV can be reduced by sodium borohydride to a pair of stable diastereomers (IV(red)()). The formation of this product is rationalized in terms of initial oxidation of 2',3', 5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine to a quinonoid diimine intermediate, 3. Nucleophilic attack at C5 of 3 by peroxynitrite leads to formation of a C5-oxyl radical species, 5, which then undergoes a series of rearrangements to yield an ylidene radical, 7. Combination of this radical species with nitrogen dioxide results in the formation of product IV.
一种新型硝化产物，是在过氧亚硝酸盐与2',3',5'-三-O-乙酰基-7,8-二氢-8-氧代鸟苷反应过程中形成的，已通过紫外/可见光谱、圆二色光谱、核磁共振光谱和质谱联用进行了表征。该化合物已被鉴定为N-硝基-N'-[1-(2,3,5-三-O-乙酰基-β-D-赤藓糖基)-2,4-二氧代咪唑烷-5-亚基]胍（IV）。在碱水解时，IV释放出硝基胍（IVa）和一种中间体，1-(2,3,5-三-O-乙酰基-β-D-赤藓糖基)-5-亚氨基咪唑烷-2,4-二酮（IVb）。该中间体最终水解为稳定的3-(2,3,5-三-O-乙酰基-β-D-赤藓糖基)草尿酸（IVc）。IV可以被硼氢化钠还原为一对稳定的非对映异构体（IV(red)()）。根据2',3',5'-三-O-乙酰基-7,8-二氢-8-氧代鸟苷最初氧化为醌型二亚胺中间体3，对该产物的形成进行了合理说明。过氧亚硝酸盐对3的C5位进行亲核攻击导致形成C5-氧自由基物种5，然后该物种经历一系列重排以产生亚甲基自由基7。该自由基物种与二氧化氮结合导致产物IV的形成。
