Disenecioyl dehydroretronecine--synthesis and acute hepatic toxicity of a pyrrolizidine alkaloid pyrrole analog.

Disenecioyl dehydroretronecine (DSDR), a semi-synthetic analog of the highly reactive pyrrole metabolites of the pyrrolizidine alkaloids, has been synthesized from disenecioyl retronecine. Rats which received 40 mg DSDR/kg body weight via the mesenteric vein showed multiple depressed areas (less than 2 mm in diameter) on the surface of the median lobe of the liver. Microscopically these areas consisted of hepatic venous occlusion, necrosis, and proliferation of fibroblasts and bile ducts in and around the portal triad. These hepatic lesions were similar to those produced by dehydroretrorcine.