Regiochemical variations in reactions of methylcubane with tert-butoxyl radical, cytochrome P-450 enzymes, and a methane monooxygenase system

Journal Article · Wed Jul 17 04:00:00 EDT 1996 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja952226l· OSTI ID:380874

Choi, S Y; Hollenberg, P F; Newcomb, M; Putt, D A ^[1]; Eaton, P E; Upadhyaya, S P; Xiong, Y ^[2]; Liu, K E; Lippard, S J ^[3]

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1. Wayne State Univ., Detroit, MI (United States)
2. Univ. of Chicago, IL (United States)
3. Massachusetts Inst. of Technology, Cambridge, MA (United States)

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.

• OSTI ID: 380874
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 28 Vol. 118; ISSN JACSAT; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

40 CHEMISTRY
55 BIOLOGY AND MEDICINE
BASIC STUDIES
BUTOXY RADICALS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CYTOCHROMES
ENZYMES
HYDROXYLATION
ORGANIC COMPOUNDS
OXYGENASES
STEREOCHEMISTRY
SYNTHESIS