SYNTHESIS OF VITAMIN B12 MODELS

维生素B12，以其辅酶的形式，是一系列 11个酶催化的转化。其中，有三种酶： β-甲基天冬氨酸变位酶、甲基丙二酰-SCOA变位酶和甲基丙二酸甲酯 变位酶具有特殊的意义，因为它们催化碳骨架 在有机中还没有类似物的重排 化学反应。此外，这一系列中还有四种氨基变位酶，它们 也缺乏良好的先例。在本方案中，化学非酶模型 将探索反应，目的是解开 维生素B12的作用。 为探索氢提取而设计的新模型，以及 氨基变位酶和β-甲基天冬氨酸变位酶重排将是 检查过了。甲基柠檬酸变位酶的~(13)C标记研究 将进行重新安排。特别努力将致力于 质谱学作为烷基化合物分析工具的进一步发展 钴胺系列。自由基中间体的可能中间性 将使用模型进行探索。三氯甲烷的立体化学研究 将进行甲基利他酸变位酶催化的重排。

Vitamin B12, in the form of its coenzyme, is a cofactor in a series of eleven enzyme-catalyzed transformations. Of these, three enzymes: Beta-methylaspartate mutase, methylmalonyl-SCoA mutase and methylitaconate mutase are of special interest because they catalyze carbon-skeleton rearrangements for which there have been no analogues in organic chemistry. In addition, there are four amino mutases in this series which also lack good precedent. In this proposal, chemical nonenzymic model reactions will be explored with the aim of unravelling the mechanism of action of vitamin B12. New models designed to explore the hydrogen abstraction, and new models for the amino mutase and Beta-methylaspartate mutase rearrangements will be examined. Carbon-13 labelling studies of the methylitaconate mutase rearrangement will be carried out. Special effort will be devoted to the further development of mass spectrometry as an analytical tool in the alkyl cobalamin series. The possible intermediacy of free radical intermediates will be explored using models. Stereochemical studies of the methylitaconate mutase catalyzed rearrangement will be conducted.