Development of New Synthetic Chemistry Using Metalloenzymes

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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.