The mechanism of oxidation of allylic alcohols to alpha,beta-unsaturated ketones by cytochrome P450.
The oxidation of cyclohex-2-en-1-ol, a simple model substrate for allylic alcohols, is catalyzed by several P450 isoenzymes and leads exclusively to cyclohex-2-en-1-one. No double bond epoxidation or C(4) hydroxylation have been observed. The large primary kinetic isotope effect measured using [2H]-1-cyclohex-2-en-1-ol is consistent with an at least partially rate limiting breaking of the C(1)-H bond. The mass spectrometric analysis of cyclohex-2-en-1-one obtained from [18O]cyclohex-2-en-1-ol has established that a gem-diol intermediate is involved, even if a dual hydrogen abstraction pathway may contribute to the reaction.
Bellucci
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Dipartimento di Chimica Bioorganica, Università di Pisa, Italy.
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Pucci
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Gervasi
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D000498:Allyl Compounds / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003903:Deuterium; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007659:Ketones / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D010103:Oxygen Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
D000498:Allyl Compounds; D007659:Ketones; D010103:Oxygen Isotopes; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium