Desaturase reactions complicate the use of norcarane as a mechanistic probe

ORGN 81

Dharmika S. P. Lansakara-P, dpathi1@uic.edu1, R. Esala P. Chandrasena1, Hye-Yeong Kim1, Martin Newcomb, men@uic.edu1, Stephen J. Lippard, lippard@lippard.mit.edu2, Laurance G. Beauvais2, Leslie J. Murray, lesjm@MIT.EDU2, Viviana Izzo2, Paul F. Hollenberg, phollen@umich.edu3, and Minor J. Coon4. (1) Department of Chemistry, University of Illinois at Chicago, 845, West Taylor Street, Room 4500 (SES), Chicago, IL 60607, (2) Department of Chemistry, Massachusetts Institute of Technology, Building 18 Room 524, 77 Massachusetts Institute of Technology, Cambridge, MA 02139, (3) Department of Pharmacology, University of Michigan, 1150 W. Medical Center Dr, 1301 MSRB III, Ann Arbor, MI 48109-0632, (4) Department of Biological Chemistry, The University of Michigan, Ann Arbor, MI 48109
We report that norcarane was oxidized by iron-containing enzymes in desaturase reactions that give 2-norcarene and 3-norcarene in addition to oxygenated products. The norcarenes were then oxidized to give secondary products, which complicate mechanistic probe studies of norcarane as the substrate. The product profiles from oxidation of norcarane, 2-norcarene, and 3-norcarene by four cytochrome P450 enzymes, CYP2B1, CYPΔ2E1, CYPΔ2E1-T303A, and CYPΔ2B4, and three diiron containing enzymes, soluble methane monooxygenase, toluene monooxygenase, and phenol hydroxylase were determined. Most of the products were identified by GC and GC-mass spectrometry comparisons to authentic samples synthesized independently. More than 20 oxidation products were identified from norcarane. The putative radical-derived product, 3-hydroxymethylcyclohexene, and putative cation-derived product, cyclohept-3-enol, from oxidation of norcarane co-elute with other oxidation products on low polarity GC columns. The limiting values for lifetimes of radical intermediates produced in the enzyme-catalyzed oxidation reactions are shorter than previously deduced from norcarane oxidation studies.

 

Process R&D, Physical Organic Chemistry, Heterocycles, Aromatics, Metal-Mediated Reactions
8:00 PM-10:00 PM, Sunday, March 25, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Organic Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007