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.
Indole C2N skeleton
Quinoline nucleus after transformation from indole
Quinoline CgN skeleton
Pyrroloindole C10N2 skeleton
Iboga Cg skeleton
Corynanthe Cg skeleton
Aspidosperma C9 skeleton Figure 32. The L-tryptophan-supplied nucleus during synthesis.
The synthesis of alkaloids from L-ornithine starts with decarboxylation by the Pyridoxal Phosphate (PLP) to putrescine (Figure 33) and putrescine metylation by S-Adenosylmethionine (SAMe) to N-methylputrescine. The SAM is a naturally occurring reaction, when the departing groups convert
Carboline C8NC3N skeleton
L-methionine to S-adenosylmethionine. In this process a positively charged sulphur is produced and facilitates the nucleophilic reaction. By the activity of diamine oxidase, the N-methyl-A1-pyrrolinium cation is formed and after that the first alkaloid, hygrine. From hygrine, by way of acetyl CoA, hydrolysis and intramolecular Mannich reactions, other pyrrolidine and tropane alkaloids are synthesized: cuscohygrine, hyoscyamine or tropinone, tropine and cocaine. The Mannich reaction involves the combination of an amine, an aldehyde or a ketone with a nucleophilic carbon. This reaction is typical in alkaloid synthesis, and can be written as follows:
The synthesis of tropine from tropinione requires dehydrogenase NADPH+. Similarly, the synthesis of cocaine requires the Mannich reaction, SAM and NADPH+. Putrescine is a biogenic amine. Other biogenic amines also participate in alkaloid synthesis, for example cadaverine in the case of lysine alkaloids. Aniszewski et al.214 drew attention to the fact that the various biogenic amines
that actively participate in the biosynthetic process of alkaloids play a role in the equilibrium between basic nitrogen compounds. Moreover, enzyme participation in pyrrolidine and tropane alkaloid synthesis has also been noted. From the L-ornithine, and alternatively also from L-arginine pyrrolizidine alkaloids are synthesized (Figure 34). The L-arginine, alternative pyrrolizidine precursor is based on its ability to change into L-ornithine, and alternatively into putrescine, via coenzyme pyridoxal phosphate (PLP) and agmatine. In the synthetic pathway to homospermidine, which is the first pyrrolizidine alkaloid in this synthesis chain, two molecules of putrescine are condensed by the enzyme NAD+ into imine before NADH converts it to homospermidine. From homo-spermidine, the synthesis chain continues across oxidative and base formation, and the Mannich reactions, to synthesize other alkaloids, such as retronecine and its diester senecionine. This synthesis pathway is also characteristic for heliotri-dine, laburine, lycopsamine and indicine-N-oxide. All these alkaloids contain the pyrrolidine nucleus, which is derived from ornithine or its precursors and postcursors.
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