Enzyme-catalysed synthesis and reactions of benzene oxide/oxepine derivatives of methyl benzoates.
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.
Boyd
Derek R
DR
School of Chemistry and Chemical Engineering, Queen's University Belfast, Belfast, BT9 5AG, UK. dr.boyd@qub.ac.uk
Sharma
Narain D
ND
Harrison
John S
JS
Malone
John F
JF
McRoberts
W Colin
WC
Hamilton
John T G
JT
Harper
David B
DB
D001565:Benzoates / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D003510:Cyclohexanes / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D010082:Oxepins / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry
D001565:Benzoates; D003510:Cyclohexanes; D010082:Oxepins; D014230:Triazoles; C053540:4-phenyl-1,2,4-triazoline-3,5-dione; C044605:methyl benzoate; C023372:benzene oxide