CHEMISTRY OF BIOLOGICALLY RELEVANT QUINONE IMINES

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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.