Y-Coniceine

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... 

The piperideine derivatives have not been studied as extensively as the analogous pyrrolines (151,152). The imino structure has been established, for example, for the alkaloid y-coniceine (146) (46). The great influence of conjugation on the structure is seen with l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline (47), possessing an enamine structure, whereas the analogous 1-methyl derivative (48) possesses an imine structure according to infrared spectra (152,153). 

Conditioning chamber la 87,129,131 y-Coniceine 15188 Coniferyl alcohol 15 401 Coniine 15 188... 

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.

Pharmacologically, the properties of all three alkaloids are very similar, except y-coniceine is more stimulatory to autonomic ganglia and VV-methyl coniine has a greater blocking effect (Fodor and Colasanti, 1985). 

A situation analogous to that of the pyrroline derivatives also exists, according to spectroscopic data, with N-unsubstituted piperideine compounds. There is little experimental data because A 2-piperideines have not been studied as extensively as the analogous pyrrolines. The A structure has been established for some aliphatically substituted piperideines, e.g., J1(8)-hexahydropyrindene,12,13 J1(10)-octahydro-quinoline,13 and the alkaloid y-coniceine.14,15 According to conformational considerations, structures other than A piperideine could be expected more frequently in the piperideine series. The thia analog16 3 occurs in the amino form as shown by infrared spectral data and the estimation of active hydrogen. 

If the amino group forms part of the ketone, as it does with y-87, 88 and 8-amino-ketones,89,90 heterocyclic enamines are obtained. 1,2-Dialkyl-J2-pyrrolines and 1,2-dialkyl-J2-piperideines (15) are formed from secondary amino groups, whereas primary amino groups 91 lead to 2-alkyl-J pyrrolines and 2-alkyl-J -piperideines. Gabriel90 used the suitably substituted phthalimidoketone for the synthesis of the alkaloid y-coniceine (15 R = H, R = n-Pr, n = 2). 

The validity of the reported incorporation of A -piperideine and its 2-carboxy-derivative into y-coniceine (3), which is clearly in conflict with an acetate derivation for coniine, must be further doubted as incorporation of A -piperideine in hemlock could not be repeated, nor was any trace of this compound found during " C02 experiments. ... 

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. 

Feeding Conium maculatum to pregnant gilts led to newborn pigs with a high incidence of cleft palate. Analysis of the alkaloid content of plant samples determined that y-coniceine (162) was the responsible alkaloid. Thus, 162, like 160, is teratogenic in livestock [435]. 

The hemlock alkaloid conhydrinone (164), along with y-coniceine (162), was identified in Aloe ballyi [437],... 

CoNiuM. y-Coniceine is the principal alkaloid in young plants of Conium macviatum L., especially in the leaves. It is still the chief constituent of leaves in two-year plants, but coniine dominates in the flowers and fruits. During ripening coniceine disappears and JV -methyl-coniine is predominant (261, 356). 

Coniceines, CgHisN. Altogether six isomeric coniceines are obtained from the alkaloids of Conium maculaium only one of which, -y-coniceine, actually occurs in the plant. 

Hofmann (130) has described three methods for the preparation of a-coniceine, but these yield different products. The action of fuming hydrochloric acid on conhydrine produces the tertiary base a-coniceine, whereas the effect of alkali on iodoconhydrine and that of sulfuric acid on bromoconiine produce -coniceine and 5-coniceine respectively (132). If, on the other hand, bromoconiine is treated with alkali, y-coniceine is obtained. /3-Coniceine is the main product of the dehydration of conhydrine with phosphoric anhydride and pseudoconiceine is obtained as a product of the dehydration of pseudoconhydrine (191). 

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