Products from Enzyme-Catalyzed Oxidations of Norcarenes

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• 作者：Martin Newcomb ; Dharmika S. P. Lansakara-P. ; Hye-Yeong Kim ; R. Esala P. Chandrasena ; Stephen J. Lippard ; Laurance G. Beauvais ; Leslie J. Murray ; Viviana Izzo ; Paul F. Hollenberg ; Minor J. Coon
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：February 16, 2007
• 年：2007
• 卷：72
• 期：4
• 页码：1128 - 1133
• 全文大小：154K
• 年卷期：v.72,no.4(February 16, 2007)
• ISSN：1520-6904

文摘

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 secondaryoxidation products from the norcarenes complicate mechanistic probe studies employing norcarane asthe 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 byseveral enzymes were determined. Most of the products were identified by GC and GC-mass spectralcomparison to authentic samples produced independently; in some cases, stereochemical assignmentswere made or confirmed by 2D NMR analysis of the products. The enzymes studied in this work werefour cytochrome P450 enzymes, CYP2B1, CYP2E1, CYP2E1 T303A, and CYP2B4, and three diiron-containing enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath),toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) fromPseudomonas stutzeri OX1. The oxidation products from the norcarenes identified in this work are2-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 inlow yields in the oxidations. In matched oxidations, 3-norcarene was a better substrate than 2-norcarenein terms of turnover by factors of 1.5-15 for the enzymes studied here. The oxidation products found inenzyme-catalyzed oxidations of the norcarenes are useful for understanding the complex product mixturesobtained in norcarane oxidations.