Chemical Model Studies on the Mutagenesis of Benzofurane Dioxetanes in the Ames Test: Evidence for the Benzofuran Epoxide as Ultimate Mutagen (EN)

Adam, W. (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας (EL)

Adam, W. (EN)

The synthesis of the first benzofuran epoxide 1 was achieved by epoxidation of the benzofuran la with dimethyldioxirane and alternatively by deoxygenation of the benzofuran dioxetane 2a with sulfides. This labile epoxide formed with nucleophiles such as water, methanol, thiophenol, and imidazole the corresponding adducts 13a-16a. In contrast to epoxide 3a, the dioxetanes 2 required acid catalysis (CF3C02H) for the addition of water, methanol, and azide ion to give the corresponding adducts 511; in the absence of nucleophiles the allylic hydroperoxides 8 were formed. The decomposition of benzofuran dioxetanes 2 in the polar, ptotic solvents water and methanol afforded not only the expected cleavage products 4 but also the 1,3-dioxols 5, the spiroepoxide dimer 6a, and the 1,4-dioxines 7. An intramolecular electron-transfer mechanism is postulated for the formation of the spiroepoxide, which subsequently dimerizes to 6a or rearranges into 5 and 7. Only the benzofuran epoxide 3a, besides the benzofuran dioxetanes 2, was mutagenic in the Salmonella typhimurium strain TA100. Therefore, we implicate the epoxide 3a as the ultimate mutagen responsible for the high mutagenic activity observed with dioxetane 2a in the Ames test. We postulate that in the oxidative metabolism of polycyclic arenes and heteroarenes the corresponding epoxides are generated from the intermediary dioxetanes by deoxygenation with sulfides. (EN)

Πανεπιστήμιο Ιωαννίνων

Ιδρυματικό Αποθετήριο Ολυμπιάς

Σχολή Θετικών Επιστημών

Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

ΑΠΟΘΕΤΗΡΙΟ "ΟΛΥΜΠΙΑΣ"

Τμήμα Χημείας

J. Am. Chem. Soc. (EN)

Αγγλική γλώσσα

1991

http://pubs.acs.org/doi/abs/10.1021/ja00021a029

http://olympias.lib.uoi.gr/jspui/handle/123456789/10056

American Chemical Society (EN)