Progress toward the asymmetric total synthesis of Diazonamide A

ORGN 199

Erick B. Lezzi,, Chemistry, University of Pittsburgh, Chevron Science Center, 219 Parkman Avenue, Pittsburgh, PA 15260 and Peter Wipf,, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260.
Diazonamide A is a complex natural product that was isolated from the marine ascidian Diazona Angulata in 1991. This novel and highly strained molecule contains a unique polyheteroaromatic array and macrolactam subunit, and has shown potent cytotoxic activity against several tumor cell lines with IC50 values < 15 ng mL-1. To date, several groups have accomplished the total synthesis of the molecule, yet an asymmetric route is still lacking. Previous work within the Wipf group has focused on the construction of the C10 quaternary center via an intramolecular Heck cyclization in the presence of chiral ligands. Although the aforementioned method demonstrates potential, the current route is designed to utilize a chiral auxiliary to induce the asymmetry at the C10 center during the Heck cyclization.