SYNTHESIS OF DERIVATIVES OF POLYNUCLEAR AROMATIC

这项拟议工作的目标是合成高度纯化的、良好的- 表征的化合物可能在研究中有用处 与致癌有关的生物过程。其中一些化合物可能 致癌物，例如亚硝胺，如烟草特有的致癌物 4-(甲基亚硝胺-(3-吡啶)-L-丁酮)。有些可能是新陈代谢 中间体，例如3，4-二氢-反式-3，4-二羟基-7，12-二甲基苯 (A)-菲，它是苯系物代谢转化的中间产物 7，12-二甲基苯并(A)菲对强致癌物质的作用 Anti-1，2-anhydro-trans-3，4-dihydroxy-7，12-dimethyl1，2，3，4-tetrahydrobenz (A)蒽。一些化合物可能表现出高度的致突变性和 已知接触过人类，但缺乏致癌数据，例如， 在大约40%的人口的粪便中出现的粪便中的菲五烯 它们是已知的最具诱变性的化合物之一。这个 在粪便中发现的低浓度以及高度不稳定的 这些化合物几乎不可能分离出足够的数量 从自然来源进行研究将确定 化合物的致癌效力。

The objective of the proposed work is to synthesize highly purified, well- characterized compounds that may have utility in the study of the biological processes involved in carcinogenesis. Some of the compounds may be carcinogens, e.g., nitrosamines such as the tobacco-specific carcinogen 4-(methylnitrosaminoI-(3-pyridyl)-l-butanone. Some may be metabolic intermediates,.e.g., 3,4-dihydro-trans-3, 4-dihydroxy-7, 12-dimethylbenz (a)-anthracene, which is an intermediate in the metabolic conversion of 7,12-dimethylbenz(a)anthracene to the potent ultimate carcinogen anti-1,2-anhydro-trans-3,4-dihydroxy-7,12-dimethyl1,2,3,4-tetrahydrobenz (a)anthracene. Some compounds may have demonstrated high mutagenicity and have a known exposure to humans but carcinogenesis data are lacking, e.g., the fecapentaenes, which occur in the feces of about 40% of the population on a western diet and are among the most mutagenic compounds known. The low concentrations found in the feces along with the high instability of the compounds make it virtually impossible to isolate sufficient quantities from natural sources to conduct studies that will determine the carcinogenic potency of the compounds.