SYNTHESIS OF VITAMIN B12 MODELS

维生素B12，以其辅酶的形式，是一种必需的辅因子 十二种酶催化的一系列反应。谷氨酸变位酶，甲基- 丙二酰辅酶A变位酶和甲基丙二酸变位酶表现突出。 兴趣，因为它们催化碳骨架重排， 在有机化学中还没有类似的东西。甲基丙二酰辅酶A 琥珀酰辅酶A重排在哺乳动物系统中具有至关重要的作用； 这是身体将丙酸转化为琥珀酸的方式，导致 生化代谢的主流。在这项建议中，该机制由 这些重排发生的原因将使用模型和 酶系统。 合成了一种新的甲基丙二酰辅酶A体系模型。 添加自由基陷阱以测试自由基的发生 中间体。这项测试也将适用于酶系统。在……里面 此外，一种新的、合成的丙二酸盐结合分子将被用于研究 模型重排的可逆性。为了方便 研究谷氨酸变位酶的功能和结构，该基因将被 克隆的。然后，在供应足够的纯酶的情况下，机械和 将启动结构研究。自由基与碳负离子 谷氨酸-甲基天冬氨酸重排的中间体将是 探索并将开发出一个非常成功的希夫碱模型。 基于表面活性剂的模型将检查它们对我们的 了解一些史无前例的自由基迁移反应。

Vitamin B12, in the form of its coenzyme, is an obligatory cofactor in a series of twelve enzyme catalyzed reactions. The glutamate mutase, methyl- malonyl-CoA mutase and methylitaconate mutase enzymes are of outstanding interest because they catalyze carbon-skeleton rearrangements for which there have been no analogues in organic chemistry. The methylmalonyl-CoA to succinyl-CoA rearrangement is of crucial import in mammalian systems; it is the way the body converts propionate to succinate, leading into the main stream of biochemical metabolism. In this proposal, the mechanism by which these rearrangements occur will be explored using both model and enzymic systems. A new model for the methymalonyl-CoA system has been synthesized with an appended free radical trap to test for the occurrence of radical intermediates. This test will also be applied to the enzyme system. In addition, a new, synthetic malonate binding molecule will be used to study the reversibility of the model rearrangement. In order to facilitate the study of the function and structure of glutamate mutase, the gene will be cloned. Then, with adequate supplies of pure enzyme, mechanistic and structural studies will be initiated. Free radical and carbanion intermediates in the glutamate-methylaspartate rearrangement will be explored and a very successful Schiff base model will be developed. Surfactant-based models will be examined for their impact on our understanding of some unprecedented free radical migration reactions.