Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison). A mixture of two different compounds, picrotoxin occurs naturally in the fruit of the Anamirta cocculus plant, although it can also be synthesized chemically. Due to its interactions with the inhibitory neurotransmitter GABA, picrotoxin acts as a stimulant and convulsant. It mainly impacts the central nervous system, causing seizures and respiratory paralysis in high enough doses. Chemical structure and synthesis Picrotoxin is an equimolar mixture of two compounds, picrotoxinin (C15H16O6; CAS# 17617-45-7) and picrotin (C15H18O7; CAS# 21416-53-5). Of the two compounds, picrotin is less active. Picrotoxin occurs naturally in the fruit of the Anamirta cocculus, a climbing plant from India and other parts of Southeast Asia. The plant is known for its large stems of white wood and sweetly-scented flowers. It produces small stone fruits, Cocculus indicus, which are typically dried. Currently, there are as many as five total syntheses of picrotoxinin—one of which was published as recently as June 2020 by the Shenvi lab at Scripps. This synthesis, like most for this molecule involved the use of carvone as a stereochemical template. The strategy employed the quick formation of the polycyclic core, followed by the manipulation of oxidation states of key carbon atoms in order to produce the target molecule. Some research suggests that it can be made by the cyclofunctionalization of cycloalkenyl systems. Under kinetically controlled conditions, this process generally results in exo cyclization and forms bridged ring systems like those found in picrotoxin. Additionally, several syntheses have been proposed for picrotoxinin and picrotin, the two molecules that make up picrotoxin. In 1980, a process to convert picrotoxinin to picrotin was discovered. This synthesis begins by treating picrotoxin with trifluoroacetic anhydride in pyridine to separate the components. In 1988, researchers from Tohoku University in Japan completed a total stereoselective synthesis of both (-)-picrotoxinin and (-)-picrotin beginning with (+)-5β-hydroxycarvone. In this synthesis, eight asymmetric centers were stereoselectively prepared on a cis-fused hydrindane ring system using several different reactions: a Claisen rearrangement to introduce the quaternary center, an organoselenium-mediated reduction of an epoxy ketone, and a stereospecific construction of a glycidic ester. The last steps of this process are shown below. Picrotoxin has also been used as