Fluoranthene: synthesis and mutagenicity of four diol epoxides

Abstract

The syntheses of diol epoxides of the mutagenic hydrocarbon fluoranthene are described. Standard methodology is applied to the synthesis or targets, but fails for the synthesis of some targets. It has been shown that, two diol epoxides can be assembled by a route utilizing stereoselective, directed epoxidations. Simple molecular orbital calculations have been used to predict the reactivity of the diol epoxides in their opening to triol carbocations. Specific diol epoxides are predicted to be substantially more reactive than their isomers. A more reactive pair of diol epoxides may yield carbocations capable of alkylating cellular genetic material. This prediction is borne out in terms of the relative mutagenicity of the diol epoxides in a bacterial screen. The syntheses and mutation assay of six possible metabolites of fluoranthene (dihydrodiols and diol epoxides) are discussed in this report.