Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy

Aetokthonotoxin has recently been identified as the cyanobacterial neurotoxin causing Vacuolar Myelinopathy, a fatal neurologic disease, spreading through a trophic cascade and affecting birds of prey such as the bald eagle in the USA. Here, we describe the total synthesis of this specialized metabolite. The complex, highly brominated 1,2'-biindole could be synthesized via a Somei-type Michael reaction as key step. The optimised sequence yielded the natural product in five steps with an overall yield of 29 %.

Automated summary

Aetokthonotoxin has been identified as the cyanobacterial neurotoxin causing Vacuolar Myelinopathy, a fatal neurologic disease affecting birds of prey such as the bald eagle in the USA. The total synthesis of this specialized metabolite was achieved in five steps with an overall yield of 29% through key steps like the Somei-type Michael reaction.