Application of a 6pi-1-azatriene electrocyclization strategy to the total synthesis of the marine sponge metabolite ageladine A and biological evaluation of synthetic analogues.

A 12-step synthesis of the angiogenesis inhibitory marine metabolite ageladine A is reported. The key steps include a 6pi-1-azatriene electrocyclization for formation of the pyridine ring and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a chloroimidazopyridine. In addition, an assessment of the biological activity of a variety of synthetic analogues of ageladine A prepared during this synthesis is described.