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Author Choi, S. Y. ♦ Hollenberg, P. F. ♦ Newcomb, M. ♦ Putt, D. A. ♦ Eaton, P. E. ♦ Upadhyaya, S. P. ♦ Xiong, Y. ♦ Liu, K. E. ♦ Lippard, S. J.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword CHEMISTRY ♦ BIOLOGY AND MEDICINE, BASIC STUDIES ♦ ORGANIC COMPOUNDS ♦ HYDROXYLATION ♦ SYNTHESIS ♦ BUTOXY RADICALS ♦ CHEMICAL REACTIONS ♦ CYTOCHROMES ♦ ENZYMES ♦ OXYGENASES ♦ STEREOCHEMISTRY ♦ CARBOXYLIC ACIDS
Abstract Reactions of methylcubane (1) with the tert-butoxyl radical (t-BuO{sup .}), with cytochrome P-450 enzymes, and with a methane monooxygenase (MMO) system have been studied. 2-Methylcubanecarboxylic acid (9b) is a new compound prepared from cubanecarboxylic acid. The key synthetic reactions were (1) metalation and subsequent iodination of the 2-position of (diisopropylcarbamoyl)cubane to effect the initial functionalization, (2) lithium-for-iodine exchange and methylation followed by reduction to give 2-methyl-l-[(diisopropylamino)methyl]-cubane, and (3) dimethyldioxirane oxidation of this amine to give 9b. Reaction of 1 with t-BuO{sup .} in the presence of 2,2,5,5-tetramethylisoindole-N-oxyl radical (TMIO{sup .}) at 40-55{degree}C gave mainly cube-substituted products in confirmation of the report that hydrogen atom abstraction by the electrophilic alkoxyl radical at low temperature occurs at the cubyl C-H positions. In a competition experiment at 42{degree}C, methylcubane was at least 3.5 times more reactive toward t-BuO{sup .} than cyclohexane, indicating that the cubyl positions in 1 are >= 40 times more reactive than the methyl positions in 1 (per hydrogen) toward the alkoxyl radical. Oxidation of 1 by enzymes gave alcohol products that were converted to their acetate derivatives for identification and quantitation. Microsomal cytochrome P-450 enzymes from rat and the rat purified P-450 isozyme CYP2B1 hydroxylated 1 at all positions, whereas the reconstituted MMO system from Methylococcus capsulatus (Bath) hydroxylated l only at the methyl position. 78 refs., 1 tab.
ISSN 00027863
Educational Use Research
Learning Resource Type Article
Publisher Date 1996-07-17
Publisher Place United States
Journal Journal of the American Chemical Society
Volume Number 118
Issue Number 28


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