Substituent elimination from p-substituted phenols by cytochrome P450 ipso-substitution by the oxygen atom of the active species

研究成果: Article

51 引用 (Scopus)

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When various p-substituted phenols (substituent = NO2, CN, CH2OH, COCH3, COPh, COOH, F, Cl, and Br) were incubated with rat liver microsomes, the substituent was eliminated to produce hydroquinone, and the reaction was inhibited by CO and a cytochrome P450-specific inhibitor. In the case of p- cresol (substituent = CH3), p-toluquinol was formed instead of hydroquinone. Experiments using 18O2 proved that the elimination is accompanied with ipso-substitution by the oxygen atom of the active species in cytochrome P450. These results are similar to those in a cytochrome P450 chemical model system (Ohe, T., et al., Tetrahedron Lett. 42, 7681-7684, 1995), implying that the model is a good mimic of cytochrome P450. Substrates that lack a hydroxy group, namely p-substituted toluenes, did not undergo the reaction, thus indicating that a hydroxy group at the p-position to the eliminated substituent is necessary for this pathway. This is the same as the result obtained with the cytochrome P450 model. Finally, to elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group with several substrates. Results indicated that the mechanism of the substituent elimination can be divided into two types: the substituent is eliminated as an anion or as a cation.

元の言語English
ページ(範囲)116-122
ページ数7
ジャーナルDrug Metabolism and Disposition
25
発行部数1
出版物ステータスPublished - 1997 1

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Phenols
Cytochrome P-450 Enzyme System
Reactive Oxygen Species
Substitution reactions
Atoms
Chemical Models
Toluene
Liver Microsomes
Substrates
Carbon Monoxide
Liver
Anions
Cations
Rats
Experiments
hydroquinone

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

これを引用

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