Dibenz anthracene 5,6-oxide

Boyd and co-workers interest in the properties of arene oxide metabolites has led them to undertake investigations into the synthesis and isomerization of such compounds (e.g., dibenz[ , ]anthracene 3,4-oxide 27, phenanthrene 3,4-oxide 28, triphenylene 1,2-oxide 29, and dibenz[ ,f]anthracene 1,2-oxide 30 (Figure 4)) <2001J(P1)1091>. 

Dibenz[yellow-green colour (due to other pentacyclic impurities) has been removed by crystn from benzene or by selective oxidation with lead tetraacetate in acetic acid [Moriconi et al. J Am Chem Soc 82 3441 7960]. 

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. 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

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 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. 

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. 

Scheme 11.27 Hydrogenation products of dibenz[a,/j]anthracene over platinum oxide in 1 1 mixture of 2,2,4-trimethylpentane and acetic acid at room temperature and atmospheric pressure.

The high-molecular-weight PAHs perylene, indeno[l,2,3-c /]pyrene, dibenz[a/ ]anthracene, benzo[g/i ]perylene and coronene are also oxidized by some fungi (Gramss et al., 1999 Zheng Obbard, 2002 Fau et al, 2003 Steffen et al., 2003 Verdin et al., 2005). Although minor amounts of... 

DIBENZANTHRACENE see DCT400 l,2 5,6-DIBENZ(a)ANTHRACENE see DCT400 DIBENZARSENOLE, 5-HYDROXY-, 5-OXIDE see ARAIOO... 

Enantiopure epoxides (3/ ,4Y)-dibenz[ 7, ]anthracene 3,4-oxide and (3iJ,4Y)-phenanthrene 3,4-oxide were synthesized via involved routes and were observed to spontaneously racemize. This racemization of arene oxides is in accordance with perturbation molecular orbital predictions based on resonance energy considerations, and presumably occurs via an electrocyclic rearrangement to the corresponding (undetected) oxepine tautomer (Scheme 17) <2001J(P1)1091>. 

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. ... 

Dibenz[d, /i]anthracene has an octanol to water partition coefficient (log Row) of 6.5 and will bioconcentrate in lower organism with less efficient mixed function oxidase systems. Dibenzo[a,/ ]anthracene is poorly absorbed via the gastrointestinal track, being excreted primarily unchanged with the feces. The majority of absorbed portion will distribute to the kidney and liver where it is oxidized to the... 

Dibenz[a,fi]anthracene is metabolically activated by the mixed function oxidase (MFO) system of the liver (P448) to form an epoxide that subsequently covalently binds to the DNA. This interaction with the DNA is believed to result in the carcinogenicity of the material. The particular area of the compound oxidized by the MFO system will result in epoxides of varying carcinogenic potency. 

Ozonation of benzo[r,s,t]pentaphene (7) followed by oxidative workup led to benzo[r,s,t]pentaphene-5,8-dione (12) (14%), phthalic acid (13) (4%), p-terphenyl-2,2, 3, 2"-tetra-carboxylic acid-2, 3 -anhydride (14) (10%), and 2-(o-car-boxyphenyl)- ,10-phenanthrenedicarboxylic acid anhydride (15) (3%), with a 56% recovery of unreacted 7, Ozonation of pentaphene (11) led to a peroxidic mixture which on oxidative workup led to 2,2 -binaphthyl-3,3 -dicarboxalde-hyde (16) (16%), 2,2 -binaphthyl-3,3 -dicarboxylic acid (17) (16%), and 13 (2%), with a 28% recovery of unreacted 11. A comparison of the reactivity to ozone of carcinogenic polycyclic aromatics benzo c]phenanthrene (1), 7,12-di-methylbenz [a] anthracene (2), 3-methylcholanthrene (3), dibenz[si,]] - (4), and dibenzlsi, ]anthracene (5), benzo Si -pyrene (6) and 7, and the noncarcinogen 11, all determined in our laboratory, leads us to conclude that there is no simple, consistent correlation between carcinogenicity, K-and L-region additivity towards ozone and the Pullmans electronic theory of carcinogenesis. 

The perfluorinated oxepin has been prepared in this manner, but the content of the oxepin in the equilibrium mixture was very low <90JA6715>. A respective fused oxepin was prepared via dibenz[aj]anthracene 3,4-oxide <90JCS(Pl)2079>. 

Dibenz[flj]anthracene-3,4-oxide together with the respective oxepin (49) are mammalian metabolites of dibenz[aj ]anthracene, their synthesis is described in <90JCS(P1)2079>. 

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