Ornithine, pyrrolidine alkaloids from

Pyrrolidine alkaloids from ornithine benzylisoquinoline alkaloids from tyrosine... 

Fig. 6.1. Some relationships between primary and secondary metabolism. The probable origins are shown of the flavonoid, phenylpropanoid and isoprenoid group of compounds. The other groups discussed in the text, the non-protein amino acids and alkaloids, arise from a number of points in primary metabolism and only the origins of the tropane and pyrrolidine alkaloids from ornithine and proline and the indole alkaloids from tryptophan are shown.

Although no experiment has yet been reported to support the idea, it seems clear that a majority of the pyrrolidine alkaloids arise from the ornithine, pu-trescine, and proline pool. This could be the case for ficine (61) and isoficine (62), vochysine (63), and phyllospadine (64) but also of the Darlingia alkaloids, which share common features with hygrine this assertion probably also holds for the ruspolinone (25) and odorine-roxburghlin (59) families. Peripentadenine, isolated from a plant of the family Elaeocarpaceae, bears resemblance to other alkaloids of the elaeocarpus type such as isoelaeocarpicine (124) (161). It cannot be excluded, however, that spermidine may be a biosynthetic intermediate instead of putrescine. The question of the origin of ant alkaloid substances remains so far without an obvious answer. 

Just as terpenes could be viewed as being formed from isoprene units, alkaloids can be viewed as being derived from amino acids. Four amino acids give rise to important classes of alkaloids. As shown in Table 28.1, the pyrrolidine alkaloids are derived from the amino acid ornithine (not one of the 20 standard amino acids), the piperidine alkaloids from lysine, the isoquinoline alkaloids from tyrosine, and the indole alkaloids from tryptophan. 

Pyrrolidine alkaloids are made from the amino acid ornithine... 

Pyrrolidine is the simple five-membered cyclic amine and pyrrolidine alkaloids contain this ring somewhere in their structure. Both nicotine and atropine contain a pyrrolidine ring as do hygrine and tropinone. All are made in nature from ornithine. Ornithine is an amino acid not usually found in proteins but most organisms use it, often in the excretion of toxic substances. If birds are fed benzoic acid (PI1CO2H) they excrete dibenzoyl ornithine. When dead animals decay, the decarboxylation of ornithine leads to putrescine which, as its name suggest, smells revolting. It is the smell of death . 

There are many pyrrolidine alkaloids derived from ornithine and another large family of piperidine alkaloids derived from lysine by similar pathways involving... 

Alkaloids that contain pyrrolidine and pyrrolizidine ring systems are derived from the nonprotein amino acid, L-ornithine. Cocaine (Nl) and (—)-hyoscyamine, the two important pyrrolidine alkaloids that contain a tropane ring system, have been found to occur in coca (Erythroxylon coca, Erythroxylaceae) leaves and the whole plant of the deadly nightshade (Atropa belladonna, Solanaceae). The hepatotoxic alkaloid senecionine (N2) contains a bicyclic pyrrolizidine skeleton derived from two molecules of L-ornithine. 

The piperidine alkaloids were mentioned in the chapter (p. 1418) where the pathway was described as similar to that of the pyrrolidine alkaloids . We can follow the same reactions starting from lysine instead of ornithine. The first stage produces the cyclic iminium salt fi om lysine by decarboxylation with pyridoxal. 

A number of alkaloids are derived from ornithine and lysine by decarboxylation, conversion by amine oxidases to the corresponding aldehyde, and cyclization to a 5-membered ring system (pyrrolidine alkaloids) and a 6-membered ring system (piperidine alkaloids). Several other alkaloids that coincidentally have similar structures have been discussed under the groups of alkaloids to which they are most closely related. 

Piperidine alkaloids arise from lysine in much the same way that pyrrolidine alkaloids arise from ornithine. A total of about 700 alkaloids of these two groups are known (Ver-poorte et al, 1991). The product of decarboxylation of lysine, cadaverine, generally seems to be incorporated as an unsymmetrical intermediate, but, in some instances, a symmetrical intermediate may be involved. This has been investigated by feeding [6--lysine and [2--lysine (Fig. 29.8). A pathway involving a bound form of cadaverine (25) to pyridoxal that accounts for most observed chemical data has been proposed (Spenser, 1970) (Fig. 29.8). Decarboxylation occurs with retention of configuration. 

Pyrrolidine alkaloids a group of Alkaloids (see) with simple structmes. P.a. are either derivatives of proline (e.g. stachydrin and its diastereoisomer, beto-nicin), or they are derived from a Af-methyl-2-alkyl-pyrrolidine (e.g. hygrin and cuskhydrin). The latter occur together with the tropane alkaloid with which they share the same biogenetic precursors, ornithine and acetate. 

Biosynthesis of Elaeocarpus alkaloids has not been fully clarified. A possible route in the formation of elaeocarpine entails combination of a C12 polyketide chain and pyrrolidine derived from ornithine (Fig. 5.2.2). 

For several years it was assumed that the putrescine, which forms a part of nicotine and other pyrrolidine alkaloids, arises through the action of ODC (Mizusaki et a/., 1973) and, in fact, pyrrolidine alkaloids have been classified as ornithine-derived compounds (Leete, 1980). In contrast, our investigations with tobacco callus tissue have shown that (1) changes in the ADC activity parallel changes in alkaloid levels, while changes in ODC activity do not (2) DFMA effectively inhibits the biosynthesis of nicotine and nomicotine, while DFMO is less effective and (3) the flow of from uniformly labeled arginine... 

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). 

From ornithine—tropane, pyrrolidine, pyrrolizide alkaloids, etc. 

Ornithine is a metabolically quite active amino acid, and the important precursor of pyrrolidine nucleus, which is found in pyrrolizidine alkaloids. Ornithine itself is a non-protein amino acid formed mainly from L-glumate in plants, and synthesized from the urea cycle in animals as a result of the reaction catalyzed by enzymes in arginine. 

A later one-step synthesis was designed as a biomimetic process (18). The N-methyl pyrrolidine ring in alkaloids such as nicotine is derived from ornithine via... 

N-Methyl-2-hydroxypyrroIidine (246) is derived biosynthetically from ornithine (245). It functions as a source of the N- methylpyrrolinium ion (247), which in turn functions as a precursor of alkaloids such as tropine (248). The pyrrolidine enamine of cyclopentanone undergoes an interesting ring closure reaction with DMAD, resulting in the formation of a pyrrolizine (Scheme 92) (78TL1351). 

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