Coniine

Coniine is a poisonous alkaloid found in poison hemlock and the Yellow Pitcher Plant, and contributes to hemlock's fetid smell. It is a neurotoxin which disrupts the central nervous system. It is toxic to all classes of livestock and humans; less than 0.2g (0.007oz) is fatal to humans, with death caused by respiratory paralysis. Socrates was put to death by way of this poison in 399 BC.

Synthesis


The original synthesis of this piperidine by Ladenburg started by heating methylpyridinium iodide at 300°C (not shown)to obtain 2-methyl pyridine. 2-methyl pyridine (alpha-picoline) reacts with acetaldehyde in presence of a base to 2-propenylpyridine in a Knoevenagel condensation. This intermediate was reduced with metallic sodium in ethanol to racemic (+-) coniine (reduction by hydrogen gas is also possible). Enantiopure Coniine was obtained by fractional crystallisation of the diastereoisomers of the salt obtained with (+)-tartaric acid.

Pharmacology
Coniine paralyzes muscles in the same fashion as curare. Symptoms of paralysis occur within a half hour, and death may take several hours.

There have been a number of cases of poisoning in certain regions of Italy due to the consumption of larks and chaffinches, which eat the buds of poison hemlock during April and May. Also, the alkaloid appears to have an addictive effect: goats, cows and pigs have all shown a preference for conium-containing forage (up to the point of eventual death) if they survive initial exposure.

History
Coniine was the first of the alkaloids ever synthesised (by Albert Ladenburg in 1886).

Coniine in Literature
Coniine is the poison used to kill Amyas Crale in Five Little Pigs (published in 1943), also known as Murder in Retrospect, one of Agatha Christie's Hercule Poirot mysteries.