Toxicity of Pumiliotoxin 251D and Synthetic Analogs to the Cotton Pest Heliothis virescens

A series of 13 simplified analogs of frog skin derived pumiliotoxin indolizidine alkaloids was prepared and evaluated for their toxicity to the larvae of the important cotton pest Heliothis virescens. The alkyl side chain of pumiliotoxin 251D was replaced with a variety of substituents designed to influence or restrict its conformation and its ability to act as a site of metabolic detoxification. Significantly, a substituent in the R configuration at the C-2' carbon of the side chain was required for toxicity. Computational studies suggested that this substituent may control the active conformation of the side chain. No structural modification led to a significant improvement in toxicity over the natural product