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A four-step total synthesis of the marine pyridoacridine alkaloid demethyldeoxyamphimedine (5) is presented. With an overall yield of 6.4%, this pentacyclic compound has been synthesized by utilizing only two commercial building blocks, ethyl nicotinate and 2-iodoaniline. The final cyclization step was achieved via a directed remote ring metalation with Knochel-Hauser base (TMPMgCl·LiCl) followed by intramolecular trapping of an ester group.

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Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades.

We report the synthesis of the azaoxoaporphine alkaloid sampangine (4) and a series of ring A analogues and isomers of the marine pyridoacridine alkaloid ascididemin (2). This approach starts from readily available 1‐bromo[2,7]naphthyridine (12) or 4‐bromobenzo[c][2,7]naphthyridine (5), and the ring A scaffold bearing an ester moiety is introduced by a Suzuki or Negishi cross‐coupling reaction. The final cyclization step was achieved through a directed remote ring metallation with the Knochel–Hauser base (TMPMgCl·LiCl; TMP = 2,2,6,6‐tetramethylpiperidinyl), followed by intramolecular trapping of the ester group.