CARCINOGENICITY OF LACTONES: I. THE REACTION OF 4-METHYLBUTENO- AND 4-METHYLBUTANO-γ-LACTONES WITH PRIMARY AMINES

Abstract

As the first stage in the investigations of the mechanisms of action of carcinogenic lactones, the reactions of 4-hydroxypent-2-enoic acid lactone (II, R = CH3), which is a carcinogen, and of the non-carcinogenic 4-hydroxypent-3-enoic (III, R = CH3) and 4-hydroxypentanoic (IV, R = CH3) acid lactones with methylamine and benzylamine have been studied. As expected, the carcinogenic lactone reacts to give the Michael addition products, whereas both inactive lactones undergo ring opening by nucleophilic attack at the carbonyl group. From the relative rates of reaction of the amines with the lactones it is concluded that the induction of tumors by II (R = CH3) does not involve alkylation of biological primary alkylamino groups. The proton magnetic resonance spectra of the products enable the different reaction pathways to be distinguished readily, and may provide the basis for rapid physicochemical screening of alkylation agents that are potential carcinogens.