Alkaloids, Conium

Keeler, R.F. and Balls, L.D. (1978). Teratogenic effects in cattle of Conium maculatum and conium alkaloids and analogs,. Clin. Toxicol., 12, 49-64. 

Interestingly, the anodic oxidation of N-methoxycarbonylpiperidine derivatives 41 in AcOH affords 2,3-diacethoxylated products 42. This reaction is conveniently applicable to the synthesis of Conium alkaloids such as pseudoconhydrine 28). 

Anthraquinones Naphthoquinones Phenols Flavonoids Conium alkaloids... 

Galey FD, Holstege DM, and Fisher EG (1992) Toxicosis in dairy cattle exposed to poison hemlock (Conium maculatum) in hay Isolation of Conium alkaloids in plants, hay, and urine. Journal of Veterinary Diagnostic Investigation 4 60-64. 

Moll3 gas chromatographed some Conium alkaloids and a number of other piperidine bases. 

Earlier results with C02 in hemlock have been refined and a primary role for y-coniceine in the formation of the other Conium alkaloids seems clear. A biosynthetic sequence from y-coniceine (3)— coniine (2)— iV-methylconiine is consistent with the findings. 

The mechanism of the respiratory stimulation involves the action of Conium alkaloid on the sensory elements of the carotid body. The stimulating doses are of the order of 2-5 mg./kg. in the normal dog. According to Dautrebande and Philippot (105), this stimulatory action is abolished by denervation of both carotid sinuses. 

A color test utilizing isatin for piperidine and pyrrolidine alkaloids containing the structural unit — NH—CH2—CH2— has been described (53). Coniine and conhydrine give a positive test but pseudoconhydrine, which lacks the above feature, does not. The Conium alkaloids have been separated by gas-liquid chromatography (54). 

Coniine, 2-propylpiperidine the most important of the Conium alkaloids (see), and the toxic principle of the poison hemlock, Conium maculatum, which was used in ancient Athens to put Socrates to death. The lethal dose of C. in humans is 0.5-1 g. The largest quantities of C. are found in the unripe seeds The synthesis of C. from a-picoline and paraldehyde by Ladenburg in 1886 was the first laboratory synthesis of any alkaloid. M, 127.22, m.p. -2.5 C, b.p. 166 C, [a] 7 16°. 

Conium alkaloids simple piperidine alkaloids found only in poison hemlock, Conium maculatum. The main alkaloids are Coniine (see) and y-coniceine (M, 125.22, b.p. 168°C) the secondary alkaloids are A -methyl and hydroxy derivatives of coniine. In contrast to other piperidine alkaloids, the ring system of C. a. is synthesized from acetate rather than from lysine (Fig.). 

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 —... 

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.

Panter, K.E., Gardner, D.R. and Molyneux, R.J. (1998b). Toxic and teratogenic piperidine alkaloids from Lupinus, Conium and Nicotiana species, in Garland, T. 

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. 

Quinolizidine alkaloids (QA) are thought to be typical natural products of many Leguminosae (1-3) but a few isolated occurrences have been reported also in unrelated families, e.g. Chenopodiaceae ( 1 ), Berberidaceae ( ), Papaveraceae ( ), Scrophulariaceae ( ), Santalaceae ( ), Solanaceae ( ), and Ranunculaceae (J ). These observations could indicate that the genes for QA biosynthesis are probably not restricted to the Leguminosae but are widely distributed in the plant kingdom however, they are only rarely expressed in the other families. We could support this belief by recent experiments using plant cell suspension cultures. A short-term and transientQA formation could be detected after induction even in "QA-free" species, such as Daucus, Spinacia, Conium, and Symphytum (6). 

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

Acetate-derived alkaloids Umbelliferae Conium maculatum Coniine... 

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. 

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... 

Alkaloids are widespread in plants and include some very well-known poisons (notably coniine and strychnine), hallucinogens (morphine, cocaine and muscimol) and other potentially lethal compounds that are nevertheless used in medical practice (e.g. atropine, codeine, colchicine and morphine). As indicated by the preliminary snap-shot above, alkaloids typically have names ending in -ine and which are often related to the plant source or properties. Thus, morphine was named after Morpheus (the God of sleep) and coniine derives from Conium maculatum (hemlock), the plant used in the judicial murder of Socrates (399 BC). Various chemical tests for alkaloids are used as preliminary indicators of alkaloid presence in crude plant extracts. Finally, it should be noted that alkaloids can also exist as jVoxides of the alkaloid base. 

An alkaloid obtained mainly from the fruits and leaves of hemlock, Conium maculatum (Umbelliferae). 

Coniine, a poisonous alkaloid isolated from the seeds, leaves, and roots of hemlock Conium maculatum), has been known since ancient times. Ingestion causes weakness, paralysis, and finally death. The Greek philosopher Socrates was executed by being forced to drink a potion prepared from hemlock in 339 b.c. 

The first alkaloid which we shall consider is of especial interest historically. The Greek philosopher Socrates was put to death by being compelled to drink an extract of hemlock, Conium maculatum. In the fruit and leaves of this plant there are present six different alkaloids one of which is named from the plant and is known as conine. This compound is a colorless, strongly alkaline liquid acting as a deadly poison when taken in more than extremely small doses. Physiologically it produces paralysis of the motor nerve terminations and depression of the central nervous system. 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

Conium maculatum (hemlock) contains the poisonons piperidine alkaloid, coniine, and related alkaloids, N-methyl-coniine, conhydrine, pseudoconhydrine, and gamma-coniceine. It has well-established teratogenic activity in certain animal species. 

Frank AA and Reed WM (1990) Comparative toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), in chickens, quails, and turkeys. Avian Diseases 34 433-437. 

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