Alkaloids from Ornithine

Figure 33. Synthesis of alkaloids from ornithine. Aikaioids are derived via putrescine or glutamic semialdehyde. At least two enzymes, ODL (Ornithine decarboxylase) or PDL (Pyrroline...

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.

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). 

Tobacco Alkaloids. The relatively small number of alkaloids derived from nicotinic acid (27) (the tobacco alkaloids) are obtained from plants of significant commercial value and have been extensively studied. They are distinguished from the bases derived from ornithine (23) and, in particular, lysine (24), since the six-membered aromatic substituted pyridine nucleus common to these bases apparendy is not derived from (24). 

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

The alkaloid tylophorine was synthesized from ornithine. Ornithine was first converted into 1-pyrroline which gave the alkaloid septicine 68 after several transformation steps. This alkaloid was then oxidized into tylophorine [82JCS(P1)2477]. 

The Borage plant (syn. Forget-me-not) family (Boraginaceae Lindl.) contains L-ornithine (Figure 11 and 15) derived alkaloids, such as indicine-N-oxide in the heliotrope (Heliotropium indicum) and southern hound s tongue Cynoglosum creticum) species (Table 8). Farsam et al. reported on new alkaloids from... 

The synthesis of alkaloids from L-ornithine starts with decarboxylation by the Pyridoxal Phosphate (PLP) to putrescine (Figure 33) and putrescine metylation by 5 -Adenosylmethionine (SAMe) to A-methylputrescine. The SAM is a naturally occurring reaction, when the departing groups convert... 

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). 

The tobacco alkaloids, especially nicotine, are derived from nicotinic acid (see page 311) but also contain a pyrrolidine ring system derived from ornithine as a portion of their structure. 

Hygrine.—The alkaloid hygrine (3) is an intermediate in the formation of tropane bases. Biosynthesis is from acetic acid, plausibly via acetoacetic acid (cf. Vol. 10, p. 12), and from ornithine (1), very reasonably in the manner shown in Scheme l.1,2 Acetoacetate has been confirmed as an intact precursor for hygrine in experiments with [3-14C]- and [4-14C]-acetoacetic acid in Nicandra phys-aloides. Labelling in (3) was, respectively, of C-2 and C-3, which confirms the suspected orientation of acetoacetate in hygrine (see Scheme l).3... 

The absolute configuration of (-l-)-physoperuvine, and of its N-benzoyl derivative, was determined by the positive Cotton effect around 290 nm, in the region exactly as reported5 for (R)-(+)-3-methylcycloheptanone. The racemic form accompanies the optically active one in the plant they were separated by column chromatography. Since tropane alkaloids form in vivo from ornithine via A-pyrroline,6 the biogenetic role of secotropanes is likely to be that of products of degradation rather than of intermediates in the formation of the tropane bases. 

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. 

Phenanthroindolizidine Alkaloids.—The phenanthroindolizidine alkaloids, e.g. tylophorine (14) and tylophorinine (15), are assembled in Tylophora asthmatica from fragments derived from ornithine, phenylalanine, and tyrosine (cf. Vol. 8, p. 6 Vol. 9, p. 5). The last amino-acid is the source of ring B plus C-9 and C-10. It has now been shown that dopa is a better precursor than tyrosine for this fragment. Label from [2-14C]dopa was specifically incorporated into C-10 of (14) and (15).16... 

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... 

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