Nucleophilic Opening of a Polycyclic Aromatic K-Region Epoxide

Gary H. Posner, John R. Lever

Research output: Contribution to journalArticle

Abstract

7,12-Dimethylbenz[a]anthracene (DMBA) is one of the most potent polycyclic aromatic hydrocarbon (PAH) carcinogens; 1 in fact, DMBA-induced tumors are commonly used in cancer research. Such important biological activity has been attributed to various metabolites of DMBA, including 7-(hydroxymethyl)-12-methylbenz[a]anthracene,1 2 DMBA bay-region dihydrodiol epoxides,3 and the K-region DMBA 5,6-oxide.4 Although current thinking is that DMBA bay-region dihydrodiol epoxides are the most carcinogenic metabolites, a significant role for the K-region epoxide in carcinogenesis cannot be ruled out. For example, the finding that 5-fluoro DMBA is only weakly carcinogenic led to the conclusion that the 5-position of DMBA ာis probably involved in carcinogenesis,ိ5 and DMBA 5,6-oxide was indeed shown to be capable of transforming mouse fibroblasts in vitro6 and of initiating tumors in mice.7 Recently several DMBA 5,6-oxide adducts with guanosine residues of both DNA and RNA have been reported.8 It seemed appropriate, therefore, to pursue our interest in nucleophilic opening of epoxides9 by studying the behavior of DMBA 5,6-oxide toward various nitrogen, oxygen, and sulfur nucleophiles under homogeneous and heterogeneous conditions and thus to learn more about the fundamental chemistry of K-region epoxides. We repo,. t here the results of this investigation on the synthetically useful, alumina-promoted, nucleophilic opening of DMBA 5,6-oxide as well as the surprising and perhaps biologically significant finding that under nonaqueous homogeneous conditions aniline is enormously more effective than the more basic benzylamine in adding to DMBA 5,6-oxide.

Original languageEnglish (US)
Pages (from-to)2029-2031
Number of pages3
JournalJournal of Organic Chemistry
Volume49
Issue number11
DOIs
StatePublished - Nov 1984

ASJC Scopus subject areas

  • Organic Chemistry

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