Phenanthrene epoxide structure

At first three K-region oxides were studied, those of DMBA (XI), BP (XII) and phenanthrene, the non-carcinogenic parent (XIII) the structures are shown in Figure 8. These epoxides, which were considered very reactive, were found to remain stable both in air and in the X-ray beam when in the crystalline state (82, 83). 

Figure 8. The structures of the K-region oxides of DMBA (XI) (a, b and c), BP (XII) (d) and phenanthrene (XIII) (e). Views (c), (d) and (e) are directly onto the plane of the epoxide group.

L. Lewis-Bevan, S. B. Little, J. R. Rabinowitz, Quantum Mechanical Studies of the Structure and Reactivities of the Diol Epoxides of Benzo[c]phenanthrene , Chem. Res. Toxicol. 1995, 8, 499 - 505. 

Isocyanates 345 react with phenanthrenequinone 346 and triphenylarsine oxide to give photochromic oxazines 347 (Equation 48) <1993PS(81)37>. The isocyanate can be replaced by a phosphinimine and the phenanthrene structure can also be replaced by the corresponding phenanthroline (Equation 49) <2003WO42195>. The /ra r-fused tetrahydrooxazine 349 was prepared from epoxide 348 and 2-aminoethyl sulfate (ethanolamine 0-sulfonic acid) (Equation 50) <1987AP625>. 

Since it is the smallest aromatic hydrocarbon to have a bay-region and a K-region , phenanthrene is often used as a model substrate for studies on metabolism of carcinogenic PAHs. Phenanthrene is absorbed following oral and dermal exposure. Data from structurally related PAHs suggest that phenanthrene would be absorbed from the lungs. Metabolites of phenanthrene identified in in vivo and in vitro studies indicate that metabolism proceeds by epoxidation at the 1-2, 3-4, and 9-10 carbons, with dihydrodiols as the primary metabolites. 

Lewis-Bevan, L., Little, S. B., and Rabinowitz, J. R. (1995). Quanmm mechanical studies of the structure and reactivities of the diol epoxides of benzo[c]phenanthrene. Chem Res Toxicol 8, 499—505. Lodovici, M., Akpan, V., Giovannini, L., Migliani, E., and Dolara, P. (1998). Benzo[a]pyrene diol-epoxide DNA adducts and levels of polycyclic aromatic hydrocarbons in autoptic samples from human... 

Diol, epoxide, and/or diol-epoxide metabolites structurally similar to those described for B[a]P have been reported for many PAHs, for example, naphthalene, anthracene, phenan-threne, B[a]A, benzo[c]phenanthrene, pyrene, chrysene, DB[fl,/t]A, benzo[ ]triphenylene, and DMB[a]A (983). All of these and structurally similar PAHs have been reported by Snook et al. as cigarette MSS components (3756). 

The diol epoxides (83) and (84) of the carcinogen fluoroanthene have been prepared". MO theory has been used to predict that (83) should be substantially more reactive than (84) and this has been verified by mutagenicity tests. Force field molecular structures for the fjord region diol epoxides of benzol phenanthrene (85) have revealed steric crowding which influences the relative confoimer stabilities in this system99. 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

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