Pomegranate alkaloids

The pomegranate alkaloids, pelletierine (46) and pseudopelletierine (48) as well as minor accompanying bases, have a long history as salts of tannic acid as an anthelmintic mixture for intestinal pinworms (see Antiparasitic AGENTS, ANTHELMINTICS). The alkaloids themselves (as the taimates) are obtained from pomegranate tree (Punkagranatum L.) root bark and are among the few bases named after an individual (P. J. Pelletier) rather than a plant. 

The biological activities of piperidine alkaloids are summarized as follows - The pomegranate alkaloids, like isopelletierine, have anthelminthic activity and were used primarily as a taenicide. 

Lysine-Derived Alkaloids. Just as putresciae (36) derived from ornithine (23) is coasidered the pregenitor of the aucleus fouad ia pyrrolidine-containing alkaloids, so cadavetiae [462-94-2] (44), C H 4N2, derived from lysiae (24) is the idealized pregenitor of the 1-dehydropiperidine [28299-36-7] nucleus (45), C H N, found in the pomegranate, Sedum Dobelia, Dupin, and Lycopodium alkaloids (39). 

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

Pseudopelletierine has been obtained from the bark of the pomegranate tree (Punica granatum L.).2-5 The synthesis of the alkaloid from glutaraldehyde, methylamine, and calcium acetonedicarboxylate was first achieved by Menzies and Robinson.6 The synthetic method subsequently was improved by Schopf and Lehmann,7 and others.8 9 The condensation of a dialdehyde with an amine and acetonedicar-boxylic acid to form a heterobicyclic compound (an alkaloid or alkaloid analog, usually employing mild or so-called physiological conditions) is sometimes referred to as a Robinson-Schopf synthesis. 

When not cultivated elsewhere, this family is found from southeastern Europe to the Himalayas. It is noted for the pomegranate, Punka granatum, known since biblical limes. This has long been known to be alkaloidal, and nine of 13 samples gave positive tests in this survey. 

Properties Liquid alkaloid from the root of the pomegranate. D 0.988 (20/4C), bp 195C. Soluble in water, alcohol, ether, chloroform, benzene. 

Five alkaloids have been reported as occurring in the bark of the pomegranate tree. Of these, isopelletierine, methylisopelletierine, and pseudopelletierine have been assigned satisfactory structures which have been confirmed by synthesis. The other two are pelletierine and methylpelletierine, and as already reported in Volume I, the occurrence of the latter is uncertain. Pelletierine was assigned the structure of /3-(2-piperidyl) propanal (4). Numerous attempts to synthesize a compound of this structure have failed (5-11). Although it is possible to isolate a derivative of the aldehyde, /3-(2-piperidyl) propanal itself could not be obtained. This long series of failures has raised doubts as to the existence of pelletierine or, at least, as to the correctness of its assigned structure. 

Pelletlerine Tannate. Punicine tannate. A mixture of the tan nates of the several alkaloids from pomegranate, pelletierine, methyl- and pseudopelletierine. It contains an amount of the alkaloids equivalent to not less than 20% as the hydrochloride. 

The bark of the pomegranate tree (Punica granatum L.) was first investigated by C. Tanret who isolated from it four alkaloids which he named pelletierine (204), isopelletierine, methylpelletierine, and pseudo-pelletierine (205, 206). Methylpelletierine and pelletierine were observed to be optically active while isopelletierine and pseudopelletierine were inactive. Later, Piccinini (207) found a fifth alkaloid, isomethylpelletierine in the mother liquors obtained from the preparation of pseudopelletierine. Eventually, however, Hess (208) while reinvestigating the bark obtained pseudopelletierine, Piccinini s isomethylpelletierine and a third, optically inactive base, but found no trace of Tanret s optically active methylpelletierine. He could not find any optically active alkaloids and, considering his third base identical with Tanret s isopelletierine (185) renamed the latter base pelletierine. Further, Hess and Eichel (209) considered Tanret s methylpelletierine and Piccinini s isomethylpelletierine as identical but different from methylated pelletierine and named it methyliso-pelletierine (185). 

The Piperidine Family. It was noted in section 3.2.1.2 that the piperidine ring is biosynthesized from the amino add lysine, and the example of coniine biosynthesis was given in that section. On the pathway to coniine (3.14), a highly toxic compound isolated from the hemlock tree is the ketone derivative 3.13 this happens to be the well-known alkaloid pelletierine, which is isolated from the pomegranate tree (Scheme 3.7). It has found use in the treatment of parasitic infections (called an anthelmintic agent). 

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