The Synthesis of Natural Products Containing Spirocycles

Natural products are the most important source of active biological products. This chapter presents some of the most relevant synthesis of natural products that contain spirocyclic motifs. It focuses on (+)-calafianin, pseurotin A, (–) -ushikulide A, (–) -acutumine, and (–)-spirotryprostatin. Porco's research group designed a total synthesis process in which the key step was asymmetric nucleophilic epoxidation. Hayashi et al. reported a total synthesis of pseurotin A using an acid-catalyzed hemiacetalization, followed by dehydration as key steps for the creation of the spirocenter. Osada et al. obtained spirotryprostatin B from the fermentation broth of the fungus Aspergillus fumigatus in 1996. Spirotryprostatin B is an extremelycomplex alkaloid that appears to arise biosynthetically by phenylation of a diketopiperazine derived from tryptophan and proline. These synthesesare important examples of how organic synthesis has evolved and improved to overcome the structural challenges presented by natural products.