Hemlock alkaloid

Present along with other alkaloids in the hemlock extract used to poison Socrates)... 

Coniine (12), impHcated by Plato in the death of Socrates, is the major toxic constituent of Conium maculatum L. (poison hemlock) and, as pointed out eadier, was apparendy the first alkaloid to be synthesized. For years it was thought that coniine was derived from lysine (24), as were many of its obvious relatives containing reduced piperidine nuclei and a side chain, eg, peUetierine (46). However, it is now known (99) that coniine is derived from a polyketooctanoic acid [7028-40-2] (138), CgH QO, or some other similar straight chain analogue. 

The common hemlock, Conium maculatum, contain five alkaloids. Power and Tutin found a similar mixture in fool s parsley, and a volatile alkaloid resembling coniine i.s stated to occur in certain aroids. According to Svagr, water hemlock Cicuta virosa) owes its poisonous properties to toxin and not to cicutine, a name sometimes used as a synonym for coniine. The toxic properties of hemlock juice have been known ftom very early times thus it was the chief ingredient in the poison administered to criminals by the Greeks. The leaves and the unripe fruits are the parts used in medicine. The following are the names and formulae of the alkaloids —... 

Billing 7 has provided a scheme for distinguishing between the hemlock bases and other alkaloids, such as sparteine, nicotine and lobeline. 

Of the total alkaloids of hemlock isolated by the method of Chemnitius and fractionally distilled, the portion boiling up to 190° contains most of the coniine, -y-coniceine and A -methylconiine, the eonhydrine and... 

Pyridine Group. Piperine, Piperovatine, Leucenol, Mimosine, Alkaloids of Ricinus communis, Foenugrec, vy eca Nut, Hemlock, Lobelia, Tobacco (Nicotiana spp.). Anabasis aphylla, Pomegranate Root Bark. ... 

Caffeine occurs in tea leaves, coffee beans, and cola nuts. Morphine is obtained from unripe opium poppy seed pods. Coniine, extracted from hemlock, is the alkaloid that killed Socrates. Fie was sentenced to death because of unconventional teaching methods teacher evaluations had teeth in them in ancient Greece. 

The profound physiological effects of alkaloids have been known for centuries. For example, Socrates was put to death with an extract of hemlock, which contains a poisonous alkaloid, coniine. Other alkaloids have long been valued for their beneficial medical effects. Examples include morphine (a painkiller), quinine (used to treat malaria), and atropine (used to treat Parkinson s disease and in eye drops that dilate the pupils). 

Poison-hemlock also has historical significance to researchers because coniine was the first alkaloid discovered, in 1827, and was first synthesized in 1886 (Landenburg, 1886, reviewed in Panter and Keeler, 1989). 

Figure 2.2 Three piperidine alkaloid teratogens from Conium maculatum (poison-hemlock) (a) coniine, (b) y-coniceine, and (c) A-methyl coniine, with accompanying LD50 as determined in a mouse bioassay.

In addition to lupines, poison-hemlock and Nicotiana spp., other plant species of the genera Genista, Prosopis, Lobelia, Cytisus, Sophora, Pinus, Punica, Duboisia, Sedum, Withania, Carica, Hydrangea, Dichroa, Cassia, Ammondendron, Liparia, and Colidium contain potentially toxic and teratogenic piperidine alkaloids. Many plant species or varieties from these genera may be included in animal and human diets (Keeler and Crowe, 1984). 

Banter, K.E. and Keeler, R.F. (1989). Biperidine alkaloids of poison hemlock (Conium maculatum), in Cheeke, B.R., Ed., Toxicants of plant origin, Vol. I Alkaloids, CRC Bress, Boca Raton, pp. 109-132. 

Neurotoxic - death Poison hemlock (Conium maculatum) Coniine - neurotoxic alkaloid -poison used by Socrates... 

Piperidine alkaloids such as coniine and (—)-coniceine are very poisonous. They occur in hemlock (Conium maculatum L.), known as a very toxic plant. One of the characteristics of these piperidine alkaloids is smell. Moreover, they are neurotoxins which have acute effects such as chronic toxicity. 

Reynolds, T. 2005. Hemlock alkaloids from Socrates to poison aloes. Phytochemistry, 66 1399-1406. 

L6pez, T. A., Cid, M. S. and Bianchini, M. L. 1999. Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock. A review. Toxicon, 37 841-865. 

Bowman, W. C. and Sanghvi, I. S. 1963. Pharmacological actions of hemlock (Conium maculatum) alkaloids. Journal of Pharmacy and Pharmacology, 15 1-25. 

Heterocycles which are not biosynthesized in humans, but which are natural products produced by other life forms, are very important in the history of drug design. This is particularly true of alkaloids containing a piperidine ring. These include coniine (8.87, extracted from poison hemlock, Conium maculatum, a member of the Umbelliferae carrot family), atropine (from Atropa belladonna and other genera of the Solanaceae plant family the plant was called belladonna [ beautiful woman ] since it was used by... 

Coniine Coniine or (5 )-2-propylpiperidine, molecular formula CgHnN, is a poisonous alkaloid found in the hemlock poison and the yellow pitcher plant (Sarracenia flava). Coniine contributes to the foul smell of hemlock. It is a neurotoxin, causes respiratory paralysis and is toxic to all classes of livestock and humans. In 399 BC, Socrates was put to death hy this poison. 

The solanaceae alkaloids and other other sources of antimuscarinics affect the CNS. They can produce hallucinations in addition to their effects on the peripheral nervous system. Witchcraft of the Middle Ages produced mixtures of plants - deadly nightshade, monkshood, and hemlock among them - as "flying ointments". The combined toxins disturbed the rhythm of the heart and led to delirium which could create a sensation of rising and falling, that is, flying. 

Several cyclic imines were reduced with phenylsilane as a reducing agent in the presence of the chiral titanocene catalyst 11 followed by a workup process to give the corresponding cyclic amines in excellent ee [26]. The hydrosilylation of 2-propyl-3,4,5,6-tetrahydropyridine with (R)-ll (substrate Ti=100 l) in THF at room temperature was completed in about 6 h (Scheme 14) [29]. The reaction mixture was treated with an acid and then with an aqueous base to afford (S)-coniine, the poisonous hemlock alkaloid, in 99% ee. 

The simple piperidine alkaloid coniine from poison hemlock is not derived from lysine, but originates by an animation process and is discussed on page 381. 

The alkaloid coniine has been isolated from hemlock and purified. Its molecular formula is C8H17N. Treatment of coniine with excess methyl iodide, followed by silver oxide and heating, gives the pure (S)-enantiomer of A,A-dimethyloct-7-ene-4-amine. Propose a complete stmcture for coniine, and show how this reaction gives the observed product. 

By the end of this chapter we hope you will be able to recognize some basic classes of natural products and know a bit about their chemistry. We will meet alkaloids such as coniine, the molecule in hemlock that killed Socrates, and terpenes such as thujone, which was probably the toxin in absinthe that killed the nineteenth-century artists in Paris. 

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