Bay region

BAY 94337 — see l,2,4rTriazin-5-one, 4-amino-6-t-butyl-3-methylthio- Bay region epoxides, 7, 189 Beckmann rearrangement, 7, 34 Beirut reaction, 3, 181-184 6, 407, 425 Bemegride... 

Crews, P., Campbell, L. and Heron, E. 1977. Different chemical types of Plocamium violaceum (Rhodophyta) from the Monterey Bay Region, California. J. Phycol. 13 297-301. 

Cerniglia CE, DT Gibson, C van Baalen (1982) Naphthalene metabolism by diatoms isolated from the Kachemak Bay region of Alaska. J Gen Microbiol 128 987-990. 

DesGranges J-L, Rodrigue J, Tardif B, Laperle M. 1998. Mercury accumulation and biomagnification in ospreys (Pandion haliaetus) in the James Bay and Hudson Bay regions of Quebec. Arch Environ Contam Toxicol 35 330-341. 

Hoffman DJ, Ohlendorf HM, Mam CM, Pendleton GW. 1998. Association of mercury and selenium with altered glutathione metabolism and oxidative stress in diving ducks from the San Francisco Bay region, USA. Environ Toxicol Chem 17 167-172. 

Rattner BA, McGowan PC, Golden NH, Hatfield JS, Toschik PC, Lukei Jr RF, Hale RC, Schmitz-Afonso 1, Rice CP. 2004. Contaminant exposure and reproductive success of ospreys (Pandion haliaetus) nesting in Chesapeake Bay regions of concern. Arch Environ Contam Toxicol 47 126-140. 

Figure 2. 7-Methylbenz[a]anthracene and benzo[a]pyrene indicating those regions defined as bay regions and the structures of the corresponding bay region dihydrodiol epoxides.

Figure 4. The bay region dihydrodiol epoxide route of metabolism of benzo[a]pyrene.

The finding that BaP is highly stereoselectively metabolized to dihydrodiols and bay-region 7,8-dihydrodiol-9,10-epoxides (summarized in Figure 1) by liver microsomes from 3-methylcholanthrene-treated rats led Jerina et a . (48) to propose a model of the substrate binding site for cytochrome P-450c (Figure 7) which... 

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. 

Anthracene is noncarcinogenic and is structurally incapable of forming a bay region diol epoxide. Anthracene 1,2-dihydrodiol is most conveniently synthesized from 2-anthranol by oxidation with phenylseleninic anhydride to anthracene 1,2-dione (55) followed by reduction with NaBH in ethanol (22) or LiAlH (55). Anthracene 1,2-dihydrodiol has also been synthesized via the Prdvost reaction route... 

Chrysene is a weak tumor initiator and is inactive as a complete carcinogen (38). The 1,2-dihydrodiol is more active as a mutagen than the 3,4- or the 5,6-dihydrodiols. The biological data support the hypothesis that the principal active metabolite of chrysene is the bay region anti-1,2-diol-3,4-epoxide (58). 

Epoxidation of 10 with m-chloroperbenzoic acid yielded the chrysene anti-1,2-diol-3,4-epoxide, whereas similar reaction of 11 gave a mixture of the corresponding anti and syn diol epoxides in a 5 3 ratio (57,59). These findings are in accord with previous observations that dihydrodiols free to adopt the diequatorial conformation undergo anti stereospecific epoxidation, whereas bay region diaxial dihydrodiols yield mixtures of anti and syn diastereomers. The syn-... 

Benzo(c)phenanthrene (BcP) is exceptionally weak or inactive as a carcinogen in experimental animals (51). On the other hand, the bay region anti diol epoxide of BcP (14) exhibits high tumor initiating activity on mouse skin (65). 

Epoxidation of the 3,4-dihydrodiol with m-chloroperbenzoic acid afforded stereospecifically the corresponding anti diol epoxide (74). Peracid oxidation of the bay region 1,2-dihydrodiol gave a mixture of the anti and syn diol epoxide diastereomers. Assignment of the major isomer as syn was made through analysis of the NMR spectra of the acetates of the tetraols formed on hydrolysis of the individual diol epoxides (42). Peracid oxidation of the 10,11-dihydrodiol is reported to yield the corresponding anti diol epoxide (12). However, it is likely for steric reasons that the syn isomer is also formed. 

Syntheses of the 1,2- and 7,8-dihydrodiols of 5-MC have been described (60,87,103). The 1,2-dihydrodiol (30a) is most efficiently prepared from l-hydroxy-5-MC (29a) by Method IV (87), with the difference that an a-phenol is employed rather than a 8-phenol as in previous examples. Oxidation of 29a with (KSO NO furnished a single isomeric quinone identified as 5-MC 1,2-aione (Figure 18). Formation of an ortho rather than a para quinone in the oxidation of an a-phenol with Fremy s reagent is unusual. Apparently the bay region methyl group serves to sterically block oxidative attack in the adjacent bay region site. Reduction of 5-MC 1,2-dione with NaBH in ethanol gave 5-MC 1,2-dihydrodiol. 

Epoxidation of the 1,2- and 7,8-dihydrodiols of 5-MC with m-chloroperbenzoic acid furnished the corresponding anti diol epoxides 26 and J27. Compound 26 was the first diol epoxide bearing a methyl group in the same bay region as the epoxide function to be synthesized. While the diol epoxide 26 is relatively reactive (104), it is more stable than the structurally analogous DMBA 1,2-diol-3,4-epoxide (21) it was obtained as a white crystalline solid. 

The Bay Region Theory of Polycyclic Aromatic Hydrocarbon Carcinogenesis... 

Mutagenicity data for benz[a]- and benz[c]acridine dlol epoxides and tetrahydroepoxldes reveals a deactivating effect of nitrogen dependent upon its position relative to the epoxide. Benz[a]acridine bay region dlol and tetrahydroepoxldes have significantly reduced mutagenicities relative to their... 

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