Enzyme-catalysed synthesis and reactions of benzene oxide/oxepine derivatives of methyl benzoates

Derek Boyd, Narain Sharma, J.S. Harrison, John Malone, W.C. McRoberts, John Hamilton, David Harper

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17 Citations (Scopus)

Abstract

A series of twelve benzoate esters was metabolised, by species of the Phellinus genus of wood-rotting fungi, to yield the corresponding benzyl alcohol derivatives and eight salicylates. The isolation of a stable oxepine metabolite, from methyl benzoate, allied to evidence of the migration and retention of a carbomethoxy group ( the NIH Shift), during enzyme-catalysed ortho-hydroxylation of alkyl benzoates to form salicylates, is consistent with a mechanism involving an initial arene epoxidation step. This mechanism was confirmed by the isolation of a remarkably stable, optically active, substituted benzene oxide metabolite of methyl 2-( trifluoromethyl) benzoate, which slowly converted into the racemic form. The arene oxide was found to undergo a cycloaddition reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to yield a crystalline cycloadduct whose structure and racemic nature was established by X-ray crystallography. The metabolite was also found to undergo some novel benzene oxide reactions, including epoxidation to give an anti-diepoxide, base-catalysed hydrolysis to form a trans-dihydrodiol and acid-catalysed aromatisation to yield a salicylate derivative via the NIH Shift of a carbomethoxy group.
Original languageEnglish
Pages (from-to)1251-1259
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume6
Issue number7
DOIs
Publication statusPublished - Feb 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

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    Boyd, D., Sharma, N., Harrison, J. S., Malone, J., McRoberts, W. C., Hamilton, J., & Harper, D. (2008). Enzyme-catalysed synthesis and reactions of benzene oxide/oxepine derivatives of methyl benzoates. Organic and Biomolecular Chemistry, 6(7), 1251-1259. https://doi.org/10.1039/b718375e