SEMI-RIGID CONJUGATED POLYENES AS MODEL ANTICARCINOGENS

β-胡萝卜素是一种普遍存在的植物多烯，也是植物中的正常成分。 人类饮食。 几项流行病学研究已经确定， 是一种有效的保护剂，对肺癌，除其他形式。 的 该项目的长期目标是创造更有效的 脂溶性多烯型抗癌剂。 近距离目标是 β-胡萝卜素防龋的化学机制， 是实现长远目标的合理依据。 通常，双键上的取代基（烯）以顺式或顺式排列。 反式形式（异构体），可以遭受顺式-反式相互转化， 激烈 在这个过程中，在中间位置短暂地存在一个双自由基 阶段 但由于它的寿命太短， 作为一种非常有效的自由基陷阱， 是衰老、突变和致癌的主要因素。 随着多烯中连接在一起的双键数目的增加， 顺反异构体的数量随着2N和顺反互变的增加而增加 发生得更快，温度更低。 β-胡萝卜素，一种多烯 11个双键，理论上有256个异构体，但通常是 以全反式β-胡萝卜素的形式提供。 一个具体的目标是发现在多低的温度下， β-胡萝卜素的形式可以相互转化。 如果这些变化能够发生 在生理温度下，然后一种（或多种）顺式β-胡萝卜素， 而不是全反式异构体，因为通常认为，可能是他们的真实 抗癌剂 如果它们在更低的温度下发生， 短暂的双自由基可能会在细胞膜上有自己的生命， 细胞，并作为自由基的高效陷阱。 近期目标是合成具有七个和六个碳原子的半刚性多烯。 9个双键，它们的顺反互变动力学研究 以及通过氢化热测定它们的热化学性质 为了弥合经过充分研究的系统之间的差距， 五个双键和十一个β-胡萝卜素。 三个结果 可以预期的是：一个更精确的估计的可访问性的 β-胡萝卜素的临界双自由基捕获能力; 全反式β-胡萝卜素可能异构为顺式异构体假说 在体温下;并且，根据结果，警告调查 哪种异构体或哪几种异构体实际上是活性的问题， 抗癌剂 第二个目标是促进已知的顺式异构体的测试， 胡萝卜素

Beta-Carotene is a ubiquitous plant polyene and a normal component of the human diet. It has been established in several epidemiological studies to be a potent protective agent against lung cancer, among other forms. The long-range goal of this project is the creation of more effective anticarcinogens of the fat-soluble polyene type. The near-range goal is a chemical mechanism for the anticarinogenticity of beta-carotene that may serve as the rational basis for achieving the long-range goal. In general, substituents on a double bond (ene) are arranged in cis or trans forms (isomers) that can suffer cis-trans interconversion on being heated. In this process, a diradical exists fleetingly at the half-way stage. But for its far too short lifetime, the diradical would function as a very effective trap for the free radicals that are now widely accepted to be major contributors to aging, mutagenesis and carcinogenesis. As the number of double bonds joined together increases in polyenes, the number of cis-trans isomers increases as 2n and cis-trans interconversion occurs more rapidly and at lower temperatures. Beta-Carotene, a polyene of eleven double bonds, has in theory 256 isomer, but is commonly available as all-trans beta-carotene. A specific goal is to discover at how low a temperature the many cis, trans forms of beta-carotene can be interconverted. If these changes can occur at physiological temperature, then one (or more) of the cis beta-carotenes, and not the all-trans isomer, as is generally believed, may be their true anticarcinogenic agent. If they occur at even lower temperature, the fleeting diradicals may take on a life of their own in the membrane of a cell and serve as highly effective traps for free radicals. The immediate goal is the synthesis of semi-rigid polyenes with seven and nine double bonds, the study of kinetics of their cis-trans interconversion and the determination of their thermochemistries by heat of hydrogenations with a view to bridging the gap between the well-studied systems with three and five double bonds and the beta-carotenes with eleven. Three results can be expected: a much more precise estimate of the accessibility of the critical diradical trapping capabilities of beta-carotene; a testing of the hypothesis that all-trans beta-carotene may be isomerizing to cis isomers at body temperature; and, depending on the outcome, an alert to investigate the question of which isomer or isomers are in fact the active anticarcinogenic agents. A second goal is to facilitate the testing of the known cis isomers of beta-carotene.