Rearrangement quinone epoxides

Hulbert, P. B. Grover, P. L. Chemical rearrangement of phenol-epoxide metabolites of polycyclic aromatic hydrocarbons to quinone-methides. Biochem. Biophys. Res. Commun. 1983, 117, 129-134. 

Quinones, typical of unsaturated ketones, undergo base-catalysed epoxidation The epoxy ketone may then rearrange with the formation of a hydroxy quinone. Quinones may also act as dienophiles in the Diels-AIder reaction. This can be a useful way of constructing polycyclic ring systems (Scheme 3.54). 

Aromatic compounds may be oxidized either through epoxidation or via addition of oxygen atom from Cpd I (Scheme Id). Usually, both pathways afford more stable phenols or quinones as the end product through rearrangements and/or addition of another nucleophile. Direct abstraction of an electron from aromatic moiety is viable in the presence of strong electron-donating substituents. The oxidative metabohsm of polycyclic aromatic compounds is represented by CYPlAl in humans. 

The hydroformylation of the orf/zo-prop-2-enylphenol 81 which contains no benzylic hydroxy group gives a mixture of the open-chain aldehyde 82 and the seven-membered cyclic hemiacetal 83 in a 82 83 ratio of approximately 40 60 (equation 34) °. The ben-zofuran epoxide 85 and its valence-isomeric quinone methide 86, both readily obtainable from benzofuran 84, rearrange thermally above —20°C to form the allylic alcohol 87 and the tautomeric phenol 88 (equation 35) . ... 

Certain polycyclic aromatic hydrocarbons can be converted to their epoxides, as typified by the reaction of phenanthrene with DDO (eq 9). Aromatic heterocycles like furans and benzofurans also give epoxides, although these products are quite susceptible to rearrangement, even at subambient temperatures (eq 10). The oxidation of heavily substituted phenols by DDO leads to quinones, as shown in eq 11, which illustrates the formation of an orthoquinone. 7 The corresponding hydroquinones are intermediates in these reactions, but undergo ready oxidation to the quinones. 

The microsomal mixed-function oxidase system containing multiple forms of cytochrome P-450 is the catalytic site for the initial oxidation of BaP. The primary products are the 2,3-, 4,5-, 7,8-, and 9,10-epoxide. The 4,5-epoxide has been isolated, while the formation of the other epoxides was demonstrated indirectly (757, 754, 236, 415, 428, 482, 505, 506). Primary oxidation at the 6 position results in formation of the unstable 6-hydroxy-BaP which is further oxidized by way of the 6-oxo radical to the 1,6-, 3,6-, and 6,12-quinones 290, 291, 350, 351). The major phenolic metabolite of BaP is 3-hydroxy-BaP lesser amounts of 1-, 7-, and 9-hydroxy-BaP are also formed. These phenols are produced at least partially by nonenzymatic rearrangement of the epoxides (the NIH shift 85, 93, 164, 236, 272, 416, 422, 424, 428, 482, 505, 506). 

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