Divergent total synthesis of indolizidine-, quinolizidine-, and decahydroquinoline-type poison-frog alkaloids

The skin extracts of Neotropical poison-frogs contain a variety of lipophilic alkaloids, and over 800 alkaloids representing >20 structural classes have been isolated or detected to date. Pumiliotoxins (PTXs) and decahydroquinolines (DHQs) are the major classes of poison-frog alkaloids, and their structural diversity and pharmacological activity have stimulated considerable interest in their chemical synthesis by several groups. However, no divergent synthesis of PTXs and DHQs have been reported so far. We have achieved the divergent total synthesis of these alkaloids and were able to establish that chiral building blocks (2R,3S)-ethyl 1-allyl-3-hydroxy-6-oxopiperidine-2-carboxylate (−)-1 and (2R,6S)-1-benzyl 2-methyl 6-(acetoxymethyl)piperidine-1,2-dicarboxylate 75 are extremely useful and versatile for the synthesis of natural products, especially indolizidine, quinolizidine, and decahydroquinoline alkaloids.