Benz anthracene 5,6-oxide

The optically active benz[a]anthracene oxides (89) and (90) have been synthesized. Thermal recemization (at 293-322 K, in CDCI3) of the chiral chrysene 3,4-oxide (91) has been shown to occur via first-order kinetics, with an activation energy of 25.2 kcal mol" The results are consistent with a reaction mechanism involving an oxepine intermediate (92), as predicted by theory. 

Photoisomerization of benz[a]anthracene 3,4-oxide, triphenylene 1,2-oxide, and benz[a]an-thracene 1,2-oxide yields anthra[2,l-6]oxepin [mp 125-126 C (pentane/Et20)], phen-anthro[10,9-/r]oxepin [mp 109-110°C (hexane/Et20)], and anthra[2,1 -/joxepin [mp 70CC (dec., pentane/Et20)], respectively.12 0... 

Mahaffey WR, DT Gibson, CE Cerniglia (1988) Bacterial oxidation of chemical carcinogens formation of polycyclic aromatic acids from benz[a]anthracene. Appl Environ Microbiol 54 2415-2423. 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

As presented in Table II, no quinones are obtained with NADPH for dibenz[a,h]anthracene and benz[a]anthracene, whereas with cumene hydroperoxide a trace amount of benz[a]anthracene quinone is observed. For the PAH with low IP, quinones are formed in the presence of both cofactors. The relationship between IP and formation of quinones constitutes further evidence that these metabolites are obtained by an initial one-electron oxidation of the PAH with formation of its radical cation. 

The EH-catalyzed hydration of the enantiomers of the K-region epoxides of BaA, CR, and BcPh allows informative comparisons to be made [92 - 94], With four among the six substrates, nucleophilic attack is selective for the oxirane C-atom with (5)-configuration (Fig. 10.12). This is, for example, true for the two enantiomers of chrysene 5,6-oxide. Looking at the data in another way, it is also apparent that, irrespective of the enantiomer, nucleophilic attack occurs preferentially at C(5) for benz[a]anthracene 5,6-oxide, but at C(6) for benzo[c]phenanthrene 5,6-oxide. In other words, the regio- and... 

The ease of formation of PAH cation-radicals is related to their IP. Above a certain IP, activation by one-electron oxidation becomes unlikely because the removal of one electron by the active forms of P450 or peroxidases is more difficult. A cutoff IP above which one-electron oxidation in not likely to occur was tentatively proposed to be about 7.35 eV (Cavalieri and Rogan 1995). For example, 7,12-dimethylbenz[a]-anthracene has an IP of 7.22 eV and is extremely carcinogenic. Benz[a]anthracene has an IP of 7.54 eV and is very weak in this sense. The active carcinogenicity of dibenz[a,h]anthracene (IP 7.61 eV) is not attributable to the one-electron mechanism. It is worth noting that the one-electron transfer is only one of the operating mechanisms of carcinogenesis. 

Some PAHs may have two hydrogens at a specific carbon position, the indicated hydrogens. Such an indicated hydrogen should be mentioned by carbon number, even when it is further oxidized to a carbonyl group consider, for example, 7//-benz[rfe]anthracene (XII) and 7//-bcnz[rfe]anthraccn-7-onc (XIII, benzan-throne). 

Both procaryotic and eukaryotic microorganisms have the enzymatic potential to oxidize aromatic hydrocarbons that range in size from a single ring (e.g., benzene, toluene and xylene) to polycyclic aromatics (PC As), such as naphthalane, anthracene, phenanthrene, benzo [a] pyrene and benz [a] anthracene (Table 4.4). However, the molecular mechanisms by which bacteria and higher microorganisms degrade aromatic compounds are fundamentally different. 

The first arene oxides to be synthesized (1964) were obtained by the cyclization of appropriate seco derivatives. 0,0-Diformylbiphenyl derivatives, when treated with Mark s reagent [tris(dimethylamino)phosphine], gave arene oxides [Eq. (3)]. Thus K-region epoxides from phenanthrene and its analogs, benz[a]anthracene and its 7,12-dimethyl analog, have been prepared.34... 

Benz[a] anthracene 5,6-oxide (145) has been synthesized in 30% optical... 

As with 141, the ( + )- and (-)-benz[a]anthracene 8,9-oxides are prepared by the same sequence in optically pure form. The configuration of (—)-benz[a]anthracene 8,9-oxide (148) is unequivocally assigned as SS,9R by configurational correlation with the tetrahydrobenz[o]anthracene 149, whose absolute configuration is determined by X-ray crystallography.72... 

The major isolated mammalian liver metabolite of benz[a]anthracene, the (— )-8,9-dihydroxy-8,9-dihydroderivative, has an 81 ,91 configuration and is enzymatically derived from (+)-(8/ ,9S)-benz[a] anthracene 8,9-oxide. It may be converted to trans-(%R,9S )-dihydroxy-( 10S, 11R )-epoxy-8,9,10,11 -tetrahydrobenz [a] anthracene prior to being covalently bonded to cellular nucleic acids. 

Keller and Heidelberger131 reported the kinetics of solvolysis of 1, 30, 38, and benz[a,/i]anthracene 5,6-oxide (228). These studies were carried out mostly in the pH < 7 region where nucleophilic addition ordinarily does not take place with either K-region or non-K-region epoxides. These authors found evidence for the formation of a carbonium ion and consequently were led to believe that the cell macromolecules react with arene oxides through a carbonium ion-trapping mechanism and not by a direct nucleophilic displacement on the oxides. 

Based on this sequence, Blum et a/.158 have reported a general synthesis of unsubstituted K-region arene imines from the corresponding arene oxides. K-Imines of benz[a] anthracene, 7-methylbenz[a]anthracene, dibenz [a,/i] anthracene, and benzo[a] pyrene have been prepared. Azido alcohol formation from these oxides is generally nonregiospecific and both possible regioisomers of the azido alcohols are formed in different proportions. 

One-electron oxidation to form cation radicals is the major pathway of activation for the most potent carcinogenic PAHs, whereas oxygenation is generally a minor pathway. For benz[a]pyrene and 7,12-dimethyl benz[a]anthracene, 80% and 90%, respectively, of the DNA adducts formed by rat liver microsomes or in mouse skin arise via the cation radicals (Cavaleri Rogan 1992). 

Analytical Properties Ionically bonded to silica, this phase provides good resolution of enantiomeric quasiequatorial frans-dehydriols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives covalently bonded to silica, this phase provides good resolution of enantiomeric pairs of quasidiaxial frans-dihydrodiols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives by addition of a third solvent (chloroform) to the classical binary mixture (hexane-alcohol) of the mobile phase, resolution of enantiomers of tertiary phosphine oxides is possible Reference 31-33, 36, 37... 

Lee B-D, Flosomi M. A hybrid Fenton oxidation-microbial treatment for soil highly contaminated with benz(a)anthracene. Chemosphere 2001 43 1127-1132. 

C20H16O 7,12-dimethyl benz(a)anthracene-5,6-oxide 39834-38-3 445.65 38.688 2 32353 C20H30O2 2b, 17b-dihydroxy-2a-ethinyl-A-nor(5a)androst 1038-19-3 579.33 51.556 2... 

A number of K-region arene oxides have been detected as intermediates in the metabolism of the corresponding PAHs in liver systems for example, phenanthrene, benz[a]anthracene, pyrene, benzo [a]pyrene, and dibenz(a,h)anthracene. These K-region arene-oxide metabolites were generally only detected by trapping the radiolabeled intermediate. The arene-oxide metabolite 102 obtained from a-naphthoflavone was found to be sufficiently stable with respect to isomerization and resistant to attack by epoxide hydrolase so that it could be isolated and identified spectroscopically. ... 

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