Studies Directed Toward the Total Synthesis of Histrionicotoxin

Histrionicotoxin (HTX) is a unique alkaloid secreted from the skin glands of the arrow poison frog, Dendrobates histrionicus. This base has been found to be a highly active venom as well as a mucosal tissue irritant toward both mammals and reptiles. Syntheses of perhydrohistrionicotoxin (H12-HTX), which exhibits all of the biological activities that histrionicotoxin does, and a photoaffinity labeled derivative of H12-HTX are described. An approach to the synthesis of the cis-enyne moieties in HTX is presented. This method utilizes the stereoselective synthesis of β-hydroxy acid derivatives obtained via the boron enolates of 3-acyl-oxazolidine-2-ones. See PDF abstract for figure.