past.paper.3 - Products from Enzyme-Catalyzed Oxidations of...

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Products from Enzyme-Catalyzed Oxidations of Norcarenes Martin Newcomb,* Dharmika S. P. Lansakara-P., ² Hye-Yeong Kim, ² R. Esala P. Chandrasena, ² Stephen J. Lippard,* ,‡ Laurance G. Beauvais, Leslie J. Murray, Viviana Izzo, Paul F. Hollenberg,* and Minor J. Coon* , Department of Chemistry, Uni V ersity of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and Departments of Pharmacology and Biological Chemistry, Uni V ersity of Michigan, Medical School, Ann Arbor, Michigan 48109 men@uic.edu Recei V ed September 8, 2006 Recent studies revealed that norcarane (bicyclo[4.1.0]heptane) is oxidized to 2-norcarene (bicyclo[4.1.0]- hept-2-ene) and 3-norcarene (bicyclo[4.1.0]hept-3-ene) by iron-containing enzymes and that secondary oxidation products from the norcarenes complicate mechanistic probe studies employing norcarane as the substrate (Newcomb, M.; Chandrasena, R. E. P.; Lansakara-P., D. S. P.; Kim, H.-Y.; Lippard, S. J.; Beauvais, L. G.; Murray, L. J.; Izzo, V.; Hollenberg, P. F.; Coon, M. J. J. Org. Chem. 2007 , 72 , 1121 - 1127). In the present work, the product profiles from the oxidations of 2-norcarene and 3-norcarene by several enzymes were determined. Most of the products were identified by GC and GC - mass spectral comparison to authentic samples produced independently; in some cases, stereochemical assignments were made or confirmed by 2D NMR analysis of the products. The enzymes studied in this work were four cytochrome P450 enzymes, CYP2B1, CYP 2E1, CYP 2E1 T303A, and CYP 2B4, and three diiron- containing enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) from Pseudomonas stutzeri OX1. The oxidation products from the norcarenes identified in this work are 2-norcaranone, 3-norcaranone, syn - and anti -2-norcarene oxide, syn - and anti -3-norcarene oxide, syn - and anti -4-hydroxy-2-norcarene, syn - and anti -2-hydroxy-3-norcarene, 2-oxo-3-norcarene, 4-oxo-2- norcarene, and cyclohepta-3,5-dienol. Two additional, unidentified oxidation products were observed in low yields in the oxidations. In matched oxidations, 3-norcarene was a better substrate than 2-norcarene in terms of turnover by factors of 1.5 - 15 for the enzymes studied here. The oxidation products found in enzyme-catalyzed oxidations of the norcarenes are useful for understanding the complex product mixtures obtained in norcarane oxidations. Introduction Mechanistic probes have been used for years to reveal details about reaction mechanisms in chemistry and biology. The concept of a mechanistic probe study is that a short-lived intermediate can be revealed by a characteristic rearrangement of a probe substrate that is observed in the reaction products.
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This note was uploaded on 01/20/2012 for the course CHM 2211 taught by Professor Castalleano during the Spring '06 term at University of Florida.

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past.paper.3 - Products from Enzyme-Catalyzed Oxidations of...

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