SEMI-RIGID CONJUGATED POLYENES AS MODEL ANTICARCINOGENS

β-胡萝卜素是一种天然存在的多烯， 正常人类饮食中的抗癌剂。 目前， 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合理地创造更多的 脂溶性多烯型有效抗癌剂。 具体目标是测试一种新颖的和以前未描述的机制 其中β-胡萝卜素作为抗癌剂。 从本质上讲， 假设β-胡萝卜素作为稳定的双自由基存在，因此， 会非常适合捕捉自由基， 被认为是老化、诱变和 癌症的发展。 这一假设在量子力学中得到了初步的支持。 多烯和多烯自由基的机械理论，但需要 实验统一才能指导药理学项目 直接的目的是检查含有五个和七个的多烯 双键 他们被选中来弥合两个国家之间的差距， 研究充分的多烯与三个双键和β-胡萝卜素与 十一 从它们在热重排中的行为来看， 双自由基形式，双自由基可及性的可靠估计 β-胡萝卜素的含量。 本研究计划合成一种新的八个多烯， 半刚性结构的热化学测定 氢化，并通过 在一定温度范围内的动力学研究。 量子力学理论的定量有效性 确定，因为这将是新的双自由基机制的可行性， 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.