CHEMISTRY OF BIOLOGICALLY RELEVANT QUINONE IMINES

生物学相关醌亚胺的化学

• 批准号: 3290877
• 负责人: JOHN S SWENTON
• 金额: $ 8.21万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3290877
• 关键词: Raman spectrometry; X ray crystallography; acetylaminofluorene; aminoacid; antineoplastics; biphenylamines; catecholamines; chemical kinetics; drug adverse effect; drug carcinogenesis; drug design /synthesis /production; drug metabolism; glutathione; imines; nuclear magnetic resonance spectroscopy; nucleoside analog; oxidation; peroxidases; quinones; stereochemistry; sulfur

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.

醌亚胺和N-酰化醌亚胺的化学 由芳香族化合物的生物氧化（细胞色素P-450）产生 氮化合物（通常为酰胺）被认为在许多方面是重要的。 生物过程。 醌亚胺是氧化反应的中间体 导致黑色素形成的儿茶酚胺。 的 抗肿瘤化合物N-甲基乙酸椭圆形钙， 四环醌亚胺键，然后与核苷反应， 个氨基酸 N-酰化醌亚胺键合的化学 亲核试剂被认为参与了相关的毒性作用 使用非那西丁等止痛药。 酰化的生物氧化 对位取代的芳胺得到N-酰基喹啉亚胺。 比如说， 致癌物N-乙酰基-2-氨基芴的生物氧化 部分涉及N-酰基喹啉亚胺的形成。 的 谷胱甘肽与这种物质的亲核加成导致可溶性的 缀合物，其提供化合物从 身体 从上面的简短概述中可以明显看出，醌亚胺和 N-酰基喹啉亚胺是重要的生物中间体。 然而，在这方面， 简单醌亚胺以及醌亚胺和N-酰基醌亚胺 参与上述生物效应的药物在 它们产生的条件。 这使他们的 在许多情况下是分离的，并对其化学进行了详细的研究。 因此 在非氧化条件下制备这些中间体的方法 条件允许对其反应性进行完整的研究。 这 反过来，可以评估它们在反应中的重要性， 生物亲核试剂 目的是开发制备上述化合物的方法， 中间体，并研究其化学与亲核试剂存在于 生物系统。 了解这些化合物的反应 与亲核试剂的接触对于确定它们在生物学中的作用至关重要。 流程.