Madangamine alkaloids: Madness and tranquility

As a small class of complicated 3-alkylpiperidine alkaloids, madangamine alkaloids have received considerable interest from the synthetic community mainly due to their intriguing polycyclic architecture and their biogenetic relevance to other manzamine alkaloids. The synthetic achievements from several groups were highlighted with emphasis on the construction of the diazatricyclic core as well as the macrocycles in the individual approaches. The infancy of the biomimetic strategy leading to the keramaphidin-type alkaloids was realized in Baldwin's inaugural synthesis, followed by improvement in the recent bioinspired approach by Fürstner. The intramolecular Diels-Alder-type reaction remains a formidable challenge for biomimetic synthesis towards manzamine alkaloids. This mini-review also outlines future directions in the development of novel strategies and tactics to inherit Baldwin's legacy.