Abstract
In the course of examining the metabolism-induced binding of benzo[a]pyrene (BP) to DNA in the presence of active liver microsomes, Borgen et al. (1) made the intriguing observation that further metabolism of trans-7,8-dihydroxy-7,8-dihydro-BP resulted in much more extensive binding to DNA than that observed with two other metabolic dihydrodiols or with BP itself. Subsequently, Sims et al. (2) suggested that the facile binding of this dihydrodiol was mediated by formation of an oxide at the 9,10-double bond. Synthesis of the suspected binding agent, 7,8-dihydroxy-9,10-epoxy,7,8,9,10-tetrahydro-BP, was claimed to result from the action of m-chloroperoxybenzoic acid on the parent dihydrodiol (2). We have considered the possibility that the suspected high chemical reactivity of this diol-epoxide from BP might well be due to anchimeric assistance (3,4) by the neighboring hydroxyl group at C-7.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
A. Borgen, H. Darvey, N. Castagnoli, T. T. Crocker, R. E. Rasmussen, and I. Y. Wang, Metabolic conversion of benzo[a]pyrene by Syrian hamster liver microsomes and binding of metabolites to deoxyribonucleic Acid, J. Med. Chem. 16, 502–506 (1973).
P. Sims, P. L. Grover, A. Swaisland, K. Pal, and A. Hewer, Metabolic activation of benzo[a] pyrene proceeds by a diol-epoxide, Nature (London) 252, 326–328 (1974). P. Sims, Polycyclic hydrocarbon epoxides as active metabolic intermediates, Chap. 39, this volume.
B. Capon, Neighbouring group participation, Q. Rev. 18, 45–111 (1964).
A. J. Kirby and A. R. Ferscht, Intramolecular catalysis, in: Progress in Bioorganic Chemistry, Vol. 1 (E. T. Kaiser and F. J. Kezdy, eds.), pp. 1–82, Wiley-Interscience, New York (1971).
D. H. R. Barton and Y. Houminer, Neighbouring hydroxy-group participation in the opening of epoxides by nucleophiles, J. Chem. Soc. Chem. Commun. 1973, 839–840.
S. M. Kupchan and R. M. Schubert, Selective aklylation: A biomimetic reaction of the antileukemic triptolides, Science 185, 791–793 (1974).
D. T. Gibson, V. Mahadevan, D. M. Jerina, H. Yagi, and H. J. C. Yeh, Oxidation of the carcinogens benzo [a] pyrene and benzo [a] anthracene to dihydrodiols by a bacterium, Science 189, 295–297 (1975).
H. B. Henbest, Stereoselectivity in the reactions of cyclic compounds, Proc. Chem. Soc. (London) 1963, 159–165.
P. Chamberlain, M. L. Roberts, and G. H. Whitham, Epoxidation of allylic alcohols with peroxy-acids: Attempts to define transition state geometry, J. Chem. Soc. (B) 170, 1374–1381 (1970).
J. Booth, E. Boyland, and E. E. Turner, The reduction of o-quinones with lithium aluminum hydride, J. Chem. Soc. 1950, 1188–1190.
G. Berti, Stereochemical aspects of the synthesis of 1,2-epoxides, in: Topics in Stereo-chemistry, Vol. 7 (N. L. Allinger and E. L. Eliel, eds), pp. 93–251, Wiley-Interscience, New York (1973).
W. Cocker and D. H. Grayson, A convenient preparation of (-)-3–3,4-epoxycarane, Tetrahedron Lett. 1969, 4451–4452.
H. Yagi, O. Hernandez, and D. M. Jerina, Synthesis of (t)-7p,8a-dihydroxy9ß,10ß-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, a potential metabolite of the carcinogen benzo[a] pyrene with stereochemistry related to the antileukemic tripolides, J. Am. Chem. Soc. 97, 6881–6883 (1975).
W. P. Jencks and K. Salvesen, Equilibrium deuterium isotope effects on the ionization of thiol acids, J. Am. Chem. Soc. 93, 4433–4436 (1971).
A. H. Conney, A. W. Wood, W. Levin, A. Y. H. Lu, R. L. Chang, P. G. Wislocki, R. L. Goode, G. M. Holder, P. M. Dansette, H. Yagi, and D. M. Jerina, Metabolism and biological activity of benzo [a] pyrene and its metabolic products, Chap. 37, this volume.
D. W. Nebert, A. R. Boobis, H. Yagi, D. M. Jerina, and R. E. Kouri, Genetic differences in benzo [a] pyrene carcinogenic index in vivo and in mouse cytochrome P, 450-mediated benzo[a] pyrene metabolite binding to DNA in vitro,Chap. 12, this volume.
P. Brookes, Role of covalent binding in carcinogenicity, Chap. 54, this volume.
P. D. Lawley, D. J. Orr, and M. Jarman, Isolation and identification of products from alkylation of nucleic acids: Ethyl-and isopropyl-purines, Biochem.J. 145, 73–84 (1975).
P. Hulbert, Carbonium ion as ultimate carcinogen of polycyclic aromatic hydrocarbons, Nature (London) 256, 146–148 (1975).
D. J. McCaustland and J. P. Engel, Metabolites of polycyclic aromatic hydrocarbons. II. Synthesis of 7,8-dihydrobenzo [a] pyrene-7,8-diol and 7,8-dihydrobenzo [a] pyrene7,8-epoxide, Tetrahedron Lett. 1975, 2549–2552.
J. F. Waterfall and P. Sims, Epoxy derivatives of aromatic polycyclic hydrocarbons: The preparation and metabolism of epoxides related to benzo [a] pyrene and to 7,8- and 9,10-dihydrobenzo[a] pyrene, Biochem. J. 128, 265–277 (1972).
A. W. Wood, P. G. Wislocki, R. L. Chang, W. Levin, A. Y. H. Lu, H. Yagi, O. Hernandez, D. M. Jerina, and A. H. Conney, Mutagenicity and cytotoxicity of benzo[a]pyrene benzo-ring epoxides, Cancer Res. 36, 3358–3366 (1976).
A. M. Jeffrey, K. W. Jennette, S. H. Blobstein, I. B. Weinstein, F. A. Beland, R. G. Harvey, H. Kasai, I. Miura, and K. Nakanishi, Benzo[a]pyrene-nucleic acid derivative found in vivo: Structure of a benzo[a]pyrene tetrahydrodiol, epoxide-guanosine adduct, J. Am. Chem. Soc. 98, 5714–5715 (1976).
M. Koreeda, P. D. Moore, H. Yagi, H. J. C. Yeh, and D. M. Jerina, Alkylation of polyguanylic acid at the 2-amino group and phosphate by the potent mutagen (±)-7β-8αdihydroxy-9β,1013-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene, J. Ant Chem. Soc. 98, 6720–6722 (1976).
D. M. Jerina and J. W. Daly, Oxidation at carbon, in: Drug Metabolism (D. V. Parke and R. L. Smith, eds.), pp. 15–33, Taylor and Francis, Ltd., London (1976).
D. M. Jerina, R. E. Lehr, H. Yagi, O. Hernandez, P. M. Dansette, P. G. Wislocki, A. W. Wood, R.L. Chang, W. Levin, and A. H. Conney, Mutagenicity of benzo [a] pyrene derivatives and the description of a quantum mechanical model which predicts the ease of carbonium ion formation from diol epoxides, in: In Vitro Metabolic Activation in Mutagenesis Testing (F. J. de Serres, J. R. Bend, and R. M. Philpot, eds.), in press, Elsevier (1976).
D. M. Jerina, R. Lehr, M. Schaefer-Ridder, H. Yagi, J. M. Karle, D. R. Thakker, A. W. Wood, A. Y. H. Lu, D. Ryan, S. West, W. Levin, and A. H. Conney, Bay region epoxides of dihydrodiols: A concept which explains the mutagenic and carcinogenic activity of benzo[a]pyrene and benzo [a] anthracene, in: Origins of Human Cancer (J. D. Watson and H. Hiatt, eds.), in press, Cold Spring Harbor Laboratory (1977).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1977 Plenum Press, New York
About this chapter
Cite this chapter
Jerina, D.M., Yagi, H., Hernandez, O. (1977). Stereoselective Synthesis and Reactions of a Diol-Epoxide Derived from Benzo[a]pyrene. In: Jollow, D.J., et al. Biological Reactive Intermediates. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4124-6_40
Download citation
DOI: https://doi.org/10.1007/978-1-4613-4124-6_40
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4126-0
Online ISBN: 978-1-4613-4124-6
eBook Packages: Springer Book Archive