Coniine

Coniine persists in the meat and milk of animals that feed on poison hemlock (Frank and Reed 1990). Humans can be exposed through the food chain. For example, an individual was documented as suffering from acute renal failure after consuming wildfowl that had eaten hemlock (Scatizzi et al. 1993). Humans have also been poisoned after mistaking poison hemlock for other members of the Umbelliferae - the root for parsnip Pastinaca sativa), the leaves for parsley Petroselinum crispum) and the seeds for anise (Pimpinella anisum) (Lopez etal. 1999). 

Synonyms 2-propylpiperidine j6-propylpi-peridine cicutine conicine 

Coniine is present in all parts of the plant poison hemlock (Conium maculatum). It is the first alkaloid to be synthesized and structure determined. Because of its high toxicity, its clinical application is very limited. 

Colorless liquid darkens on exposure to light and air polymerizes boils at 166°C (330.8°F) melts at -2°C (28.4T) alkaline, pA fl 3.1 density 0.845 at 20°C (68°F) slightly soluble in water and chloroform, readily soluble in most organic solvents. 

Coniine is a highly toxic alkaloid. The toxic symptoms from ingestion are weakness, drowsiness, nausea, vomiting, mnscle contraction, and labored breathing. A high dose can cause convulsions, cyanosis, asphyxia, and death. Chronic ingestion of coniine produced adverse reproductive effects and specific developmental abnormalities in cattles. 

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R = H), and coniine (12) were isolated (16) (Table 1). But, because the science was young and the materials complex, it was not until 1870 that the stmcture of the relatively simple base coniine (12) was estabUshed (17) and not until 1886 that the racemic material was synthesized (18). The correct stmcture for strychnine (13, R = H) was not confirmed by x-ray crystallography until 1956 (19) and the synthesis was completed in 1963 (20). 

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. 

Chemical Reactivity - Reactivity with Water No reaction Reactivity with Common Materials Will corrode most metals, producing flammable hydrogen gas which can collect in coniined spaces Stability During Transport Stable Neutralizing Agents for Adds and Caustics Flush with water and rinse with dilute solution of sodium carbonate or so ash Polymerization Not pertinent Inhibitor of Polymerization Not pertinent. 

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 —... 

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... 

Coniine, CgH jN. The alkaloid was first isolated by Giesecke. but the formula was suggested by Blyth and definitely established by Hofmann. 

Constitution. When coniine is distilled with zinc dust or heated with silver acetate/ a new base, coiiyrine, CgH N, differing from coniine by six atoms of hydrogen, is formed. This on oxidation yields pyridine-2-carboxylic acid and, since it is not identical with 2-isopropylpyridine, must be 2-propylpyridine (I). When coniine is heated with hydriodic acid at 300° it yields w-octane (II). These and other observations due mainly to A. W. Hofmann, made it clear by 1885 that coniine was probably a-propylpiperidine (III), and this has been amply confirmed by other reactions of the alkaloid and by syntheses. Thus, Wolffenstein showed that on oxidation with hydrogen peroxide, coniine is converted into amino-w-propylvaleraldehyde (IV) ... 

A number of other syntheses of coniine have been effected, of which that of Diels and Alder is of special interest. The initial adduct of pyridine and methyl acetylenedicarboxylate, viz., tetraraethylquinolizine-1 2 3 4-tetracarboxylate (IX) on oxidation with dilute nitric acid is converted into methyl indolizinetricarboxylate (X). This, on hydrolysis and decarboxylation, furnishes indolizine, the octahydro-derivative (XI) of which, also known as octahydropyrrocoline, is converted by the cyanogen bromide method (as applied by Winterfeld and Holschneider to lupinane, p. 123) successively into the broraocyanoamide (XII), cyanoaraide (XIII) and dZ-coniine (XIV). A synthesis of the alkaloid, starting from indolizine (pyrrocoline) is described by Ochiai and Tsuda. ... 

Hess and Eichel have shown that d-coniine with formaldehyde and formic acid yields an active A -methyl-d-coniine, and that methylZso-pelletierine hydrazone (see p. 57) yields ZV-methyl-dZ-coniine when heated with sodium ethoxide at 150-70°. 

Conhydrine, CgHj, ON. This oxygenated alkaloid was isolated by Wertheim. It crystallises in colourless leaflets, has a coniine-like odour, can be sublimed and is strongly basic, m.p. 121°, b.p. 226°, Wd 4" 10°- It is soluble in alcohol or chloroform, moderately so in water and in ether, from which it crystallises readily. The salts are crystalline the aurichloride small rhombs or pri.sims, m.p. 133° the benzoyl derivative m.p. 132°. 

Constitution. On oxidation with chromic acid, conhydrine yields Z-piperidyl-2-earboxylic acid. It is converted into Z-coniine either by reduction of the iodo-derivative (iodoconiine), C,HijNI, formed by the action of hydriodic acid and phosphorus at 180° or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene. These and other observations indicate that the p- ygen atom must occur as a hydroxyl group, in the w-propyl side-chain in either the a- (XV) or (XVI) position, since the y-position would involve... 

Both Cushny and Dale found the amorphous gelsemium alkaloids represented by such fractions as gelseminine much more active than gelsemine. Cushny stated that gelseminine resembled coniine in action and showed a greater depressant effect on the central nervous system, but unlike coniine it exerted no pressor effect. It was also a powerful mydriatic. Dale found that 0-001 gm. of the hydrochlorides of the amorphous alkaloids injected into rabbits caused death from respiratory failure in 25 minutes, preceded by convulsions. These results are explained by the subsequent isolation from such amorphous fractions, of the potent alkaloids sempervirine and gelsemicine. 

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