CHEMISTRY OF BIOLOGICALLY RELEVANT QUINONE IMINES

醌亚胺是多种生物氧化反应的中间体， 系统，和各种角色已被假定为这些物种。 因此，在本发明中， 许多生物学上重要的胆碱酯酶的代谢是 假定涉及醌亚胺中间体和N-烷基化醌 亚胺类物质可能与长期服用氯丙嗪的副作用有关 疗法 止痛药扑热息痛的毒性归因于 一种代谢形成的醌亚胺，结合细胞大分子。 最近的研究发现，从N-甲基椭圆形的醌亚胺 乙酸作为在体内使嘌呤核苷芳基化的中间体， 因此，这种特殊的醌亚胺可能发挥重要作用 椭圆形倍半萜的抗肿瘤活性。 简单醌亚胺以及那些参与生物效应 上述提到的通常是相当不稳定的条件下，用于他们的 一代 这妨碍了对它们的隔离和更详细的研究 它们的化学、光谱学和生物学在严格控制下 条件 因此，制备和分离醌亚胺的方法 可以深入研究它们的化学和生物学。 我们的目标是开发非氧化生成醌的方法 亚胺在高度控制的条件下，在没有还原的 形式的醌亚胺，外来过量氧化剂，金属盐， 氧化或大量的亲核试剂。 这些反应 条件将允许醌亚胺以纯的形式分离， 它们的化学和生物学可以在定义明确的 条件 初步结果表明，醌的简单衍生物 通过我们开发的化学方法可以高产率合成亚胺。 在拟议的研究中，这种方法将适用于生成 生物学相关的醌亚胺，例如在生物学中形成的那些 儿茶酚胺和9-羟基-椭圆藤乙酸盐的氧化（参见 以上）。 在仔细定义的条件下对这些系统的研究将 建立产品和他们的反应速率与生物 重要的亲核试剂 醌的光谱表征 合成的亚胺将允许评价激光拉曼光谱， 研究这些中间体在体内的化学性质。

Quinone imines are intermedites in the oxidation of a variety of biological systems, and various roles have been postulated for these species. Thus, the metabolism of a number of biologically important cathecholamines is postulated to involve quinone imine intermediates, and N-alkylated quinone imines may be involved in the side effects of long-term chloropromazine therapy. The toxicity of the analgesic paracetamol has been attributed to a metabolically formed quinone imine which binds cell macromolecules. Recent studies have invoked a quinone imine from N-methylellipticium acetate as the intermediate which arylates in vivo purine nucleosides and nucleotides; thus, this particular quinone imine may play an important role in the antitumor activity of ellipticene. Simple quinone imines as well as those involved in the biological effects noted above are usually quite unstable under the conditions used for their generation. This has prevented their isolation and a more detailed study of their chemistry, spectroscopy, and biology under carefully controlled conditions. Thus, a method for preparation and isolation of quinone imines would allow an in-depth study of their chemistry and biology. Our aim is to develop methods for the non-oxidative generation of quinone imines under highly controlled conditions, in the absence of the reduced form of the quinone imine, adventitious excess oxidant, metal salts from the oxidation, or large quantities of nucleophiles. These reaction conditions will allow the quinone imines to be isolated in pure form so that their chemistry and biology can be studied under well-defined conditions. Preliminary results have demonstrated that a simple derivative of quinone imines can be synthesized in good yield via chemistry we have developed. In the proposed research this approach will be adapted for the generation of biologically relevant quinone imines such as those formed in biological oxidation of catecholamines and 9-hydroxy-ellipticenium acetate (see above). A study of these systems under carefully defined conditions will establish the products and rates of their reactions with biologically important nucleophiles. Spectroscopic characterization of the quinone imines synthesized will allow evaluation of laser Raman spectroscopy for the study of the chemistry of these intermediates in vivo.