SYNTHESIS OF DERIVATIVES OF POLYNUCLEAR AROMATIC

本工作的目标是合成高纯度，良好的- 这些化合物可用于研究 与致癌有关的生物学过程。 一些化合物可以 致癌物，例如，亚硝胺，如烟草特有的致癌物质 4-（甲基亚硝胺基）-（3-吡啶基）-1-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）-蒽，其为以下物质的代谢转化中的中间体： 7，12-二甲基苯并（a）蒽是一种潜在的终极致癌物 反式-1，2-脱水-反式-3，4-二羟基-7，1,2-二甲基-1，2，3，4-四氢苯 （a）蒽。 一些化合物可能已证明具有高致突变性， 已知暴露于人类，但缺乏致癌数据，例如， fecapentaenes，存在于约40%的人群的粪便中 是已知的最具致突变性的化合物之一。 的 粪便中发现的浓度较低，沿着的高度不稳定性 这些化合物使得分离出足够量的 从自然资源中进行研究， 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.