80433-83-6Relevant articles and documents
Conformational Effects in the Hydrolyses of Benzo-Ring Diol Epoxides That Have Bay-Region Diol Groups
Sayer, J. M.,Whalen, D. L.,Friedman, S. L.,Paik, A.,Yagi, H.,et al.
, p. 226 - 233 (2007/10/02)
Kinetics of the hydronium ion catalyzed(KH) and pH-independent (k0) hydrolyses of several benzo-ring diol epoxides, derived from polycyclic aromatic hydrocarbons, that possess bay-region trans diol groups have been investigated in 1:9 dioxane-water at 25 deg C.These epoxides are 1,2,3,4-tetrahydrobenzanthracene-1,2-diol 3,4-epoxide, 1,2,3,4-tetrahydrotriphenylene-1,2-diol 3,4-epoxide, and 9,10,11,12-tetrahydrobenzopyrene-9,10-diol 11,12-epoxide.Both possible diastereomers of the diol epoxides in which the two hydroxyl groups are trans to each other were investigated: isomer 1, in which the benzylic hydroxyl group is cis to the epoxide oxigen, and isomer 2, in which this hydroxyl group and the epoxide oxygen are trans.The corresponding tetrahydro epoxides that lack a diol group were also investigated.For comparison, isomers 1 and 2 of 1,2,3,4-tetrahydrobenzanthracene-3,4-diol 1,2-epoxide, a bay-region epoxide with a non-bay-region trans diol group, and the corresponding benzanthracene tetrahydro epoxide were also studied.The most striking feature of the reactions of the diol epoxides that possess a bay-region diol group is a reversal of the relative reactivity of isomers 1 and 2 in the k0 reaction, when compared with diol epoxides whose diol group is not in a bay region.This reversal of reactivity, which causes k0 to be larger for isomer 2 than for isomer 1 when the diol is in a bay region, is explained by changes in conformational equilibria involving the cyclohexene ring due to steric crowding of the bay-region diol.Preference of this diol group for a pseudodiaxial conformation favors a conformation of isomer 2 which the benzylic C-O bond of the epoxide is more or less aligned with the ? orbitals of the aromatic system and strongly disfavors this aligned conformation of isomer 1.Reaction via the k0 process is faster for the aligned than for the nonaligned conformer; thus for epoxides with bay-region diol groups, k0 for isomer 2 is faster than k0 for isomer 1.The pH-independent reaction of isomer 2 of 1,2,3,4-tetrahydrobenzanthracene-1,2-diol 3,4-epoxide via the aligned conformer gives, in addition to cis and trans tetraol products, substantial quantitites of a keto diol, whereas no keto diol was detected from the corresponding isomer 1.This also represents a reversal of the pattern of product formation generally observed with diol epoxides that lack a bay region in the vicinity of the diol group.Rate constants for hydronium ion catalyzed hydrolysis (kH) are much less sensitive to conformational factors than k0.The distribution of cis and trans tetraol products from hydronium ion catalyzed hydrolysis of the 1,2,3,4-tetrahydrobenzanthracene-1,2-diol 3,4-epoxides and the 1,2,3,4-tetrahydrotriphenylene-1,2-diol 3,4-epoxides can be explained by preferential pseudoaxial attack of water upon the benzylic cations formed from these epoxides.On the basis of these observations and previous findings with non-bay-region diol, bay-region epoxides, rules for predicting the effects of conformation on rates...
Synthesis of the o-Quinones and Dihydro Diols of Polycyclic Aromatic Hydrocarbons from the Corresponding Phenols
Sukumaran, K.B.,Harvey, Ronald G.
, p. 4407 - 4413 (2007/10/02)
Terminal-ring trans-dihydro diol metabolites have been implicated as the ultimate carcinogenic forms of polycyclic aromatic hydrocarbons.Synthesis of these dihydro diols from the related polycyclic phenols in two steps via oxidation to the corresponding o-quinones with either Fremy's salt or phenylseleninic anhydride followed by stereospecific reduction with lithium aluminum hydride is described.The non-K-region quinones and trans-dihydro diols of naphthalene, anthracene, phenanthrene, benzanthracene, benzopyrene, and 7,12-dimethylbenzanthracene are synthesized via this approach.Although poor yields (1-4percent) were previously reported for the reduction of non-K-region quinones, an improved experimental procedure has been developed which affords the trans-dihydro diols free of the isomeric cis-dihydro diols in generally good yields.Major byproducts are the corresponding hydroquinones, previously undetected, and the related tetrahydro diols.The latter are the major products of reduction of the poorly soluble quinones of benzopyrene and benzanthracene and are shown to arise through further reduction of the dihydro diols.Since the tetrahydro diols are convertible to dihydro diols and the hydroquinones are reoxidizable to quinones, good overall conversions of quinones to dihydro diols are attainable. trans-3,4-Dihydroxy-3,4-dihydro-7,12-dimethylbenzanthracene synthesized in these studies is the most potent tumorigenic hydrocarbon metabolite tested to date.
