CHEMISTRY OF BIOLOGICALLY RELEVANT QUINONE IMINES

喹酮亚胺和N-酰基喹酚亚胺的化学 芳香族化合物的生物氧化(细胞色素P-450) 氮化合物(通常是酰胺)被认为在许多方面都很重要。 生物过程。苯醌亚胺是氧化反应的中间产物。 导致黑色素形成的儿茶酚胺。这个 抗肿瘤化合物N-甲基椭圆剂醋酸酯被提出形成一种 然后与核苷和核苷反应的四烷基苯醌亚胺键 氨基酸。N-酰化对苯二酮亚胺与N-取代苯二酚亚胺的化学 亲核试剂被认为与相关的毒性效应有关。 使用非那西丁等止痛药。酰化废水的生物氧化 对位取代的芳香胺得到N-酰基喹酚亚胺。例如, 致癌物质N-乙酰-2-氨基荧烯的生物氧化 部分涉及N-酰基喹酚亚胺的形成。这个 谷胱甘肽与该物种的亲核加成导致可溶的 提供化合物排泄机制的结合物 身体。 从上面的简短总结中可以明显看出，对苯二酚亚胺和 N-酰基喹酚亚胺是重要的生物中间体。然而， 简单的苯醌亚胺以及苯醌亚胺和N-酰基喹酚亚胺 参与上述生物效应的在以下情况下相当不稳定 他们生成时所用的条件。这阻止了他们的 在许多情况下分离并详细研究它们的化学成分。因此，一个 非氧化性条件下制备这些中间体的方法 条件允许对它们的反应性进行完整的研究。此入站 TURN将允许评估它们在反应中的重要性 生物亲核者。 其目的是开发制备上述物质的方法 中间体，并研究它们与存在于 生物系统。对这些化合物的反应的理解 对于确定它们在生物学中的作用是必不可少的 流程。

The chemistry of quinone imines and N-acylated quinol imines resulting from biological oxidation (Cytochrome P-450) of aromatic nitrogen compounds (generally amides) is thought to be important in many biological processes. Quinone imines are intermediates in the oxidation of catecholamines leading to the formation of melanoid pigments. The anti-tumor compound N-methylellipticium acetate is proposed to form a tetracylic quinone imine linkage which then reacts with nucleosides and amino acids. The chemistry of N-acylated quinone imine linkage with nucleophiles is proposed to be involved in the toxic effects associated with analgesics such as phenacetin. The biological oxidation of acylated p-substituted aromatic amines gives N-acylquinol imines. For example, the biological oxidation of the carcinogenic N-acetyl-2-aminofluorene involves in part the formation of an N-acylquinol imine. The nucleophilic addition of glutathione with this species leads to a soluble conjugate which affords a mechanism for excretion of the compound from the body. As evident from the short summary above, quinone imines and N-acylquinol imines are important biological intermediates. However, simple quinone imines as well as quinone imines and N-acylquinol imines involved in the biological effects noted above are quite unstable under the conditions used for their generation. This has prevented their isolation in many cases and a detailed study of their chemistry. Thus, a method for preparation of these intermediates under non-oxidative conditions would allow a complete study of their reactivity. This in turn would allow an assessment of their importance in reactions with biological nucleophiles. The aim is to develop methods for the preparation of the above intermediates and to study their chemistry with nucleophiles present in biological systems. An understanding of the reactions of these compounds with nucleophiles is essential to establishing their role in biological processes.