Piperidine alkaloids pseudoconhydrine

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. 

These piperidine alkaloids have the simplest structures for alkaloids so far described. The hemlock plants are comprised of several potent alkaloids, such as coniine, y-coniceine, conhydrine, N-methylconiine, and pseudoconhydrine. These alkaloids shall now be discussed as follows. 

Biosynthesis of these compounds proceeds through a completely different route from that of the other piperidine alkaloids (Fig. 26.3). Early work pointed to y-coniceine as the first alkaloid to be formed, followed by transformation to coniine, conhydrine, and M-methylconiine. Levels of these compounds varied greatly within the plant and under different environmental conditions and between varieties. Variations were even found between 2- or 4-h periods of a day and between days. This can be surprising, when, for instance, Leete and coworkers usually fotmd coniine and conhydrine in equal amounts in their plants but on a subsequent occasion when the plants were grown in a greenhouse in the early autumn, coniine and pseudoconhydrine were the major components [44, 50-52, 68, 88]. 

The biological activities of the poison hemlock (Conium maculatum) are due to the content of piperidine alkaloids — coniine (2-propylpiperidine), y-coniceine (2n-propyl-ly-piperidine), conhydrine (2-(l- hydroxypropyl)-piperi-dine), A/-methylc(Miiine (1-methyl-2- propylpiperidine), pseudoconhydrine ((5-hydroxypropyl)-piperidine), conhydrinone ((l-oxo-propyl)-piperidine), W-methylpseudoconhydrine (5-hydroxy-l-methyl-2-propyl-piperidine), and 2-methylpiperidine. The poismiing effect of hemlock supplements by the presence of poly-p-keto acid (2,5,7-tri-oxo-octanoic acid), quercetin, kaempferol, and glycoside dioxymid [4, 12,13, 20, 52, 85, 87]. 

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). 

Mitich W (1998) Poison-hemlock (Conium maculatum L.). Weed Technol 12 194—197 Moody CJ, Lightfoot AP, Gallagher PT (1997) Asymmetric synthesis of 2-substituted piperidines. Synthesis of the alkaloids (—)-coniine and ( )-pseudoconhydrine. J Org Chem 62 746-748... 

---