SEMI-RIGID CONJUGATED POLYENES AS MODEL ANTICARCINOGENS

β-胡萝卜素是一种普遍存在的植物多烯，是 人类饮食。在几项流行病学研究中已经证实 在其他形式中，它是预防肺癌的有效保护剂。这个 这个项目的长远目标是创造更有效的 脂溶多烯类的抗癌物质。近距离的目标是 β-胡萝卜素抗衰老的化学机制可能 作为实现长远目标的理性基础。 通常，双键上的取代基(烯)以顺式或顺式排列 可发生顺式-反式相互转化的反式(异构体) 加热过的。在这个过程中，一个双自由基在半路上短暂地存在 舞台。如果不是因为它的寿命太短，双基是可以发挥作用的 作为一种非常有效的陷阱来捕捉现在被广泛接受的自由基 是衰老、突变和致癌的主要贡献者。 随着聚烯中连接在一起的双键数量的增加， 顺反异构体数目随着2n和顺反相互转化的增加而增加 在较低的温度下发生得更快。β-胡萝卜素，一种多烯 在11个双键中，理论上有256个异构体，但通常 提供全反式β-胡萝卜素。 一个具体的目标是在多低的温度下发现许多顺式、反式 各种形式的β-胡萝卜素可以相互转化。如果这些变化能够发生 在生理温度下，一种(或多种)顺式β-胡萝卜素， 而不是像人们普遍认为的那样，全反式异构体可能是它们的真实存在 抗癌剂。如果它们发生在更低的温度下， 转瞬即逝的双自由基可能会在一种 细胞，作为自由基的高效捕捉器。 近期的目标是合成具有七个和七个基团的半刚性多烯 9个双键的顺反相互转化动力学研究 用氢化热法测定它们的热化学性质 以期弥合经过充分研究的三个系统之间的差距 5个双键和11个β-胡萝卜素。三个结果 可以预期的是：更精确地估计 β-胡萝卜素的临界双自由基捕获能力； 全反式β-胡萝卜素可能异构化为顺式异构体的假说 在体温下；根据结果，发出警报进行调查 哪一个或哪些异构体实际上是活性的问题 抗癌药物。 第二个目标是促进已知的顺式异构体的测试 β-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.