Amaryllidaceae alkaloids biosynthetic pathways

The work on the biosynthesis of Amaryllidaceae alkaloids reached a peak in the period 1960-1976 with a great number of studies related with this subject. However, since then, little new work has been produced apart from the isolation of compounds predicted as biosynthetic intermediaries of a certain pathway or, more recently, a new biosynthetic proposal to obtain galanthamine (70), which differs from the initial one. 

Thus, tyramine and protocatechuic aldehyde -or derivatives of the latter- are logical components for the biosynthesis of the precursor norbelladine (85). This reaction occupies a pivotal position since it represents the entry of primary metabolites into a secondary metabolic pathway. The junction of the amine and the aldehyde results in a Schiff s base, two of which have been isolated up to now craugsodine (114) and isocraugsodine (115). The existence of Schiff s bases in nature as well as their easy conversion into the different ring-systems of the Amaryllidaceae alkaloids allow the presumption that the initial postulate about this biosynthetic pathway was correct. 

Generally, norbelladine 2 and its congeners 4 -(9-niethylnorbelladine 10 are believed to be the biosynthetic precursor in the metabolic pathway of Amaryllidaceae alkaloids [29]. 

So far, a great deal of the structurally diverse alkaloids have been isolated and identified from plants of the family Amaryllidaceae. However, given large numbers of the unexploratory plant species in this family, one can expect that more new alkaloids will be isolated from the plant species of this family in the future. In addition, although studies about biosynthesis of Amaryllidaceae alkaloids initiated as early as the 1960s, biosynthetic pathways of Amaryllidaceae alkaloids, especially those newly established scarce subgroups, are far away from complete... 

Actually there are no good definitions of alkaloids (Bate-Smith and Swain, 1966) since each one is either too narrow or too broad. Even in the restricted Winterstein and Trier definition, at least five alkaloid families exist that can be derived from different amino acids consequently, there is a need to establish the proper biosynthetic pathways to permit the application of the alkaloid character to chemotaxonomy, It has been mentioned above that canadine (berberidine) may be found in plants of six partially unrelated botanical families. This fact is not surprising when considered in relation to the biochemical investigations of canadine biosynthesis. Many reactions are necessary to convert tyrosine into canadine consequently, one might even wonder why the distribution of this alkaloid is so limited. In contrast, other plants (and even some that produce canadine) can produce many alkaloids that are derived from tyrosine but have a marked difference in structure. Tyrosine serves as the key precursor of alkaloids of the isoquinoline type, but other types of alkaloids, such as colchicine and the Amaryllidaceae and the Erythrina alkaloids, may be synthesized from this amino acid. The nucleus of an alkaloid molecule can arise from different precursors thus the indole nucleus in Erythrina alkaloids arises from tyrosine, while in brucine it comes from tryptophan (Figure 1.5). The alkaloids cinchonamine and cinchonine differ in that cinchonamine has an indole nucleus, while cinchonine (like quinine) has a quinoline nucleus however, they exist in a precursor-product relationship (that is, the quinoline type is derived from the indole type in a one-step reaction). 

The Amaryllidaceae alkaloids are restricted to the monocot family that coined their name. They are derived from one molecule of tyrosine and protocatechuic aldehyde, which originates from phenylalanine. The central intermediate of their biosynthetic pathway is norbelladine. Nearly 500 structures of Amaryllidaceae alkaloids are known, and some of them possess significant pharmacological activities (Jin, 2007) (Fig. 10). For example, the isocarbostyrils pancratistatin from the spider lily Hymenocallis littoralis) and narciclasine from Narcissus species show promising antineoplastic properties (Dumont et al., 2007 McLachlan et al, 2005). Lycorine that occurs, e.g., in Clivia, Crinum and Galanthus... 

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