ABSTRACT: Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC50 = 25 nM against PANC-1, making it a potential candi-date for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic car-bonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.
Experimental details and spectral data