Total Synthesis of the Cyanobacterial Alkaloid Nostodione A

An efficient total synthesis of the indole alkaloid nostodione A is achieved in seven steps with an overall yield of 38.6%, starting from 1,3‐cyclopentanedione and 1‐iodo‐2‐nitrobenzene. Construction of the novel 3,4‐dihydrocyclopenta[ b ]indole‐1,2‐dione tricyclic intermediate is critical to the proposed synthesis and facilitates rapid access to the natural product. The active methylene group of the tricyclic indole intermediate is harnessed to incorporate the benzylidene moiety through a Knoevenagel condensation. The robustness and scalability of the synthesis enable the preparation of a library of nostodione analogs by merely altering the aldehyde partner. Finally, although nostodione A is classified as an inactive antiproliferative molecule according to the sulforhodamine B assay, unique novel cytotoxic molecules can be easily prepared using the nostodione A framework as an innovative template.