ORGN 137

Members of the histrionicotoxin family of dendrobatid alkaloids, represented by the prototypical structure (-)-histrionicotoxin 1, are important neurological research tools that have aroused considerable interest as a result of their interesting pharmacological properties.  A low natural abundance of these alkaloids combined with a ban on collection of frogs from the family Dendrobatidae means that an efficient route to these analogs is required.

"

Two routes to the tricyclic core of histrionicotoxin have been investigated, the key steps being either a tandem hydroxylamine-alkyne cyclisation / nitrone 1,3-dipolar cycloaddition or a tandem Michael addition / [3+2]-cycloaddition.

Progress towards the total synthesis of HTX 285A 2 will be presented together with a discussion of tandem Michael addition / [3+2]-cycloaddition reactions.