MECHANISTICALLY CRYPTIC ENZYME REACTIONS

两种机械隐蔽酶催化的研究 提出了各种方法以及各种有用的、 手性标记化合物。来自美国的一种酶系统 氨基丁酸梭菌脱水4-羟基丁酰辅酶A 至E-2-丁烯基-辅酶A。这一过程似乎涉及到 去除相对非酸性的质子，因此 在机械上不寻常。拟议的研究包括确定 整体反应立体化学，评价特点 酶催化的烯丙基重排可能是 参与，并观察氟取代物的命运 底物。底物和底物类似物，由 氢和/或氟将被合成。2H和19F核磁共振 光谱学将用于分析。澄清： 机制将有助于界定结构性和机械性 一般对酶催化脱水的要求。是这样的 信息可以非常有用的预测路径。 次生代谢与外源代谢 物质，包括毒素和毒品。酶水平 环己酮氧化制己二酸的表征 由厌氧菌Paracoccus sp.还提出了NCIB 11086。 合理但史无前例的机制将得到评估， 使用标有13C和2H的底物；分析将通过 质谱学。阐明一种独特的机制可能 促进针对厌氧病原体的药物靶向。 手性标记环氧乙烷在合成α-环氧乙烷中的应用 各种有用的、标记的生物分子被提出。

The study of two mechanistically cryptic enzyme-catalyzed processes is proposed as are syntheses of a variety of useful, chirally-labeled compounds. An enzyme system from Clostridium aminobutyricum dehydrates 4-hydroxybutanoyl-CoA to E-2-butenoyl-CoA. This process appears to involve the removal of a relatively nonacidic proton and is therefore mechanistically unusual. Proposed studies include determining the overall reaction stereochemistry, evaluating characteristics of an enzyme-catalyzed allylic rearrangement that may be involved, and observing the fates of fluorine-substituted substrates. Substrates and substrate analogs, substituted with deuterium and/or fluorine will be synthesized. 2H and 19F NMR spectroscopy will be used for analyses. Elucidation of the mechanism will help to define the structural and mechanistic requirements of enzyme-catalyzed dehydrations in general. Such information can be of great utility in predicting pathways of secondary metabolism as well as metabolism of foreign substances, including toxins and drugs. Enzyme-level characterization of the oxidation of cyclohexanone to adipic acid by the anaerobe Paracoccus sp. NCIB 11086 is also proposed. Reasonable but unprecedented mechanisms will be evaluated, using substrates labeled with 13C and 2H; analyses will be by mass spectrometry. Elucidation of a unique mechanism may facilitate targeting of drugs to anaerobic pathogens. Applications of chirally-labeled oxirane to the synthesis of a variety of useful, labeled biomolecules are proposed.