A Behemoth from the Deep: The Discovery and Synthesis of Maitotoxin.

Abstract

Maitotoxin is a unique molecule that is not only the largest known secondary metabolite that is not a polymer or protein, but is also one of the most potent toxins known to date, with an LD50 of 50 ng/kg.

First isolated from Gambierdiscus toxicus in 1977 by Yasumoto et al., its structure was determined in 1993 by Yasumoto et al., and its stereochemistry in 1996 by Kishi et al. and Tachibana et al.. Although in 2006, it was called into doubt when Gallimore & Spencer (2006) argued that, based on biosynthetic theories, the stereochemistry was assigned incorrectly. Following this disagreement, Nicolaou et al. set out to prove that the originally-proposed structure was correct and undertake the total synthesis of Maitotoxin as a whole.

This paper discusses how Nicolaou et al. settled the structural dispute in 2007 and further looks at how the other fragments of Maitotoxin were synthesised during an eight-year-long synthesis project that was unfortunately cut short in the end due to a lack of funding. Finally, a plan for connecting the synthesised fragments is proposed that would allow for the completion of the Maitotoxin ring system.