Polycyclic aromatic hydrocarbons epoxide derivatives

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. 

Sayer JM, Whalen DL, Jerina DM. Chemical strategies for the inactivation of bay-region diol-epoxides, ultimate carcinogens derived from polycyclic aromatic hydrocarbons. Drug Metab Rev 1989 20 155. 

Depending on the oxidation conditions, benzene and its substituted derivatives, and polycyclic aromatic hydrocarbons may be converted to phenols and quinones. Alkoxylation and acyloxylation are also possible. Addition reactions may afford dihydrodiols, epoxides, and endoperoxides. 

Even the 1,2-dihydrodiol derivatives of polycyclic aromatic hydrocarbons are converted to the corresponding epoxydiols with MCPBA. The reaction is stereoselective only in some cases. The trans-dihydrodiols (6) give the antiepoxide (7), whereas the cfs-dihydrodiols (8) give a mixture of anti- (9) and syn-epoxy compounds (10). The anti- and syn-diol epoxides of benz[a]anthracene and benzo[a]pyrene have been prepared by this method.10... 

Analytical Properties Resolution of several enantiomers of polycyclic aromatic hydrocarbons, for example, chrysene 5,6-epoxide, dibenz[a,h]anthracene 5,6-epoxide, 7-methyl benz[a]anthracene 5,6-epoxide resolution of barbiturates, mephenytoin, benzodiazepinones, and succinimides direct separation of some mono-ol and diol enantiomers of phenanthrene, benz[a]anthrene, and chrysene ionically bonded to silica gel, this phase provides resolution of enantiomers of c/s-dihydroidiols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives having hydroxyl groups that adopt quasiequatorial-quasiaxial and quasiaxial-quasiequatorial conformation Reference 31-35... 

In 2001, ab initio, density-functional and semiempirical calculations on the reactivity of polycyclic aromatic hydrocarbon episulfides 10-22 were reported. Episulfides are predicted to open more easily than the corresponding 0-protonated derivatives, epoxides and diol epoxides <2001HCA3588>. Calculation results for the episulfide ring opening of the j -protonated compounds are shown in Table 1. 

Oesch F, Golan M. 1980. Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons. Cancer Lett 9 169-175. 

Geacintov, N.E. (1988) Mechanisms of reaction of polycyclic aromatic epoxide derivatives with nucleic adds, in Polycyclic Aromatic Hydrocarbon Carcinogenesis Structure-Activity Relationships, vol. II (eds S.K. Yang and B.D. Silverman), CRC Press, Boca Raton, EL, pp. 181-206. 

For many years applications of the Bradsher reaction were restricted due to its limited substrate scope and requirement for harsh reaction conditions. However, after the advancement of the arene oxide concept concerning the metabolism of polycyclic aromatic hydrocarbons, synthesis of all the nuclear monohydroxylated derivatives of 7,12-dimethylbenz[a]-anthracene (DMBA), diol epoxide metabolites of DMBA, and fluoro derivatives of DMBA was undertaken for carcinogenicity and mutagenicity determination studies. " Interest in the Bradsher reaction has increased greatly as a consequence of the need to construct these polycyclic aromatic hydrocarbons. Development of fluoroanthracenylmethyl cinchonidine as an efficient phase-transfer catalyst for asymmetric glycine alkylation also expanded the scope of the Bradsher reaction. ... 

Chen and Heidelberger reported the use of cell lines derived from the adult C3H mouse ventral prostate in a focus assay for studying oncogenesis in culture. Similar clones of mouse prostate cells have been used by Marquardt et ai (53,54) j-Qj. studying the carcinogenic activity of the epoxides of several polycyclic aromatic hydrocarbons. They also reported a good correlation between in vivo transformation by the antibiotics adriamycin, daunomycin, and actinomycin... 

Aromatic substances are oxidized to hydroxyderivatives and dihydroxy-derivatives. Benzene (1) is converted through an instable epoxidic form (2) to phenol (3) which is further oxidized to form pyrocatechol (4) or hydro-quinone (5). The muconic acid (6) is the terminal oxidation degree, being formed by opening the benzene ring. In this way, not only monocyclic but also polycyclic hydrocarbons are oxidized, such as quinoline, indol and coumarins. Some substances are even oxidized to water and carbon dioxide... 

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