Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy

Abstract

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 %.

Keywords: biindole-coupling; bromination; indole; natural products; total synthesis.