SEMI-RIGID CONJUGATED POLYENES AS MODEL ANTICARCINOGENS

β-胡萝卜素是一种天然产生的多烯，是一种有效的 人类正常饮食中的抗癌剂。它目前是 一项大规模流行病学研究的对象。 这个应用程序的长期目标是理性地创建更多 脂溶多烯类的有效抗癌物质。 具体目标是测试一种新的、以前未描述的机制 通过它，β-胡萝卜素起到抗癌作用。从本质上讲， β-胡萝卜素被假设为以稳定的双自由基存在，因此， 将非常适合于捕捉广泛存在的自由基 被认为是衰老、突变和 癌症的发展。这一假说在量子理论中得到了初步的支持 多烯和多烯自由基的力学理论，但需要 统一实验，然后才能指导一个药理学项目。 眼下的目标是检查含有五和七个的聚烯。 双键。他们被选中来弥合 具有三个双键的多烯和具有β-胡萝卜素 十一。从它们在热重排中的行为来看， 对偶根形式，对偶根的可及性的可靠估计 贝塔胡萝卜素将被制造出来。 这项检查计划合成一部小说中的八个多烯， 半刚性结构的热化学测定 氢化作用及其相关的双自由基的鉴定 在一定温度范围内的动力学研究。 量子力学理论的量化有效性将是 新的双自由基机制的可行性也将是确定的 β-胡萝卜素的抗癌作用。

Beta-Carotene is the naturally occurring polyene emerging as a potent anticarcinogenic agent in the normal human diet. It is presently the object of a large-scale epidemiological study. The long-range goal of this application is the rational creation of more effective anticarcinogens of the fat-soluble polyene type. The specific goal is to test a novel and previously undescribed mechanism by which Beta-carotene acts as an anticancer agent. In essence, Beta-carotene is hypothesized to exist as a stable diradical and, as such, would be eminently suited to trap the free radicals that are widely accepted to be major contributors to aging, mutagenesis, and the development of cancer. The hypothesis finds tentative support in a quantum mechanical theory of polyenes and polyenic radicals, but requires experimental unification before it can guide a pharmacological program. The immediate aim is the examination of polyenes containing five and seven double bonds. They have been selected to bridge the gap between the well-studied polyenes with three double bonds and Beta-carotene with eleven. From their behavior in a thermal rearrangement involving the diradical form, a reliable estimate of the accessibility of the diradical of Beta-carotene will be made. This examination projects the synthesis of eight polyenes of a novel, semi-rigid structure, the determination of their thermochemistry by heat of hydrogenation, and the identification of their related diradicals by kinetic study over a range of temperatures. The quantitative validity of the quantum mechanical theory will be determined, as will be viability of the new diradical mechanism for the anticancer action of Beta-carotene.