Development of New Synthetic Chemistry Using Metalloenzymes

这项研究得到了有机和 高分子化学计划。 该研究涉及 酶作为合成工具的发展， 高度控制的过程，具有相当大的经济影响。 黄博士过往的工作成果丰硕，广受好评。 烃类在失活时的选择性官能化 碳中心是最具挑战性的， 重要的化学技术问题。 发展 这些反应将为我们提供新的机会。 高价值化学品和药品的生产， 有毒废物副产品的处理。 许多金属酶 能够催化这种转化。 本研究 将集中在两个含铁的单加氧酶， 活化分子氧羟基化失活的C-H 一个是甲烷单加氧酶;另一个是 异青霉素N环化酶。 将使用甲烷单加氧酶 用于制备手性醇、环氧化物和亚砜 从中间前驱体。 异青霉素N环化酶将用于 一种新型肽抗生素的制备方法， 酶的底物将通过酰胺酶损伤制备 蛋白酶和脂肪酶催化的反应。 新型立体化学 比甲基环丙烷更紧张的自由基探针将 准备并用于研究可能的自由基机制 C-H激活的信号

This research is being supported by the Organic and Macromolecular Chemistry Program. The research involves the development of enzymes as synthetic tools which can lead to highly controlled processes of considerable economic impact. Dr. Wong's prior work has been very fruitful and well received. The selective functionalization of hydrocarbons at inactivated carbon centers is one of the most challenging and technologically important problems in chemistry. Development of such reactions will open new opportunities for the production of high-value chemicals and pharmaceuticals and for the treatment of toxic waste byproducts. Many metalloenzymes are capable of catalyzing such transformations. This research will focus on two iron-containing monooxygenases capable of activating molecular oxygen to hydroxylate inactivated C-H bonds: one is methane monooxygenase; the other is isopenicillin N cyclase. Methane monooxygenase will be used for preparation of chiral alcohols, epoxides, and sulfoxides from meso precursors. Isopenicillin N cyclase will be used for preparation of novel peptide antibiotics; the peptide substrates for the enzyme will be prepared via amidase-damaged protease and lipase catalyzed reactions. New stereochemical and radical probes more strained than methylcyclopropane will be prepared and used to investigate possible radical mechanisms of the C-H activation.