Synthetic Compounds with Toxic Properties similar to those of Pyrrolizidine Alkaloids and their Pyrrolic Metabolites

Abstract

FOR the first time, some of the toxic effects of unsaturated pyrrolizidine alkaloids on rats have been reproduced by dosing animals with synthetic compounds. Many of the naturally occurring hepatotoxic alkaloids are esters of the isomeric amino-alcohols retronecine or heliotridine with various branched chain hydroxy-acids¹. The most toxic alkaloids are cyclic diesters of retronecine¹, which are particularly resistant to enzymic hydrolysis. Because hepatotoxicity of the pyrrolizidine alkaloids has been associated with the metabolic conversion of the pyrroline to a pyrrole ring^2,3, with retention of the ester groups⁴, it was expected that simpler pyrroline esters would have similar toxic properties provided that the ester groups were resistant to enzymic hydrolysis.