Biosynthesis amaryllidaceae alkaloids

Much was already kndwn of the gross features of Amaryllidaceae alkaloid biosynthesis five years ago and in the ensuing period it has been the revelation of the intricate stereochemistry of the processes involved which has proved most interesting. Newer aspects of this work are discussed in this Report (p. 19). 

El Tahehy, A., et al.. New method for the study of Amaryllidaceae alkaloid biosynthesis using biotransformation of deuterimn-labeled precm or in tissue cultures. 

Biological Activity of Colchicine Medicinal Uses of Colchicine Use of Colchicine in Horticulture Amaryllidaceae Alkaloids Biosynthesis Biological Activity... 

Amaryllidaceae Alkaloids.—Detail has been added to the fairly thoroughly delineated pathways to the Amaryllidaceae alkaloids.75 76 11-Hydroxyvittatine (94), previously shown to be a precursor for narciclasine (96),76 has been proposed as an intermediate in the biosynthesis of haemanthamine (92) and montanine (95) following the observed specific incorporation of vittatine (93) into the two... 

Previous studies45 have demonstrated that tyrosine and phenylalanine follow separate pathways in providing the hydroaromatic C6—C2—N unit and the aromatic C6 unit of mesembrine. In this respect mesembrine follows the pattern, already established for the biosynthesis of the structurally related Amaryllidaceae alkaloids derived from O-methylnorbelladine, e.g. haemanthamine (70). The present investigation46 followed this lead and started with a reasonable working hypothesis (Scheme 12) in which the biosynthesis proceeds via O-methylnor-belladine (68) and intermediates of the crinine type such as (75). However, feeding... 

Amaryllidaceae Alkaloids.—O-Methylnorbelladine (162) and vittatine (163) are implicated as intermediates in the biosynthesis of narciclasine (164). " Loss of the two-carbon bridge from the latter could plausibly occur by a retro-Prins reaction on 11-hydroxyvittatine (165) to give (166), as shown in Scheme 18, analogy for hydroxylation of (163) coming from the biosynthesis of the related alkaloid haeman-thamine.Strong support for this pathway to narciclasine (164) was obtained when it was shown that tritiated (165) was an efficient precursor for this alkaloid.It is to be noted that collapse of a similar j8-hydroxy-amine is proposed for the biosynthesis of colchicine. 

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. 

The mesembrine alkaloids, e.g. mesembrine (97), bear a strong structural resemblance to the Amaryllidaceae alkaloids of the crinine type, e.g. haemanthamine (91), but careful investigation has shown that the only aspect of biosynthesis... 

Amaryllidaceae and Aizoceae families. Second, without use of doubly labelled precursors erroneous conclusions on mesembrine alkaloid biosynthesis would have been reached. 

Although amino-acids have been administered to plants on occasions legion in number, rarely has attention been paid to the question of whether there is any selectivity for the D- or L-amino-acid in alkaloid biosynthesis. An exception appears in work on the Amaryllidaceae alkaloids where it was shown that d- and L-tyrosine were equally well utilized in lycorine biosynthesis. The question has now been answered in Nicotiana glauca for the biosynthesis of anabasine (118) and pipecolic acid (113) from lysine. Pipecolic acid was found to be derived preferentially from the D-isomer ( 48 times better), in accord with a similar preference in intact rats and corn seedlings, whereas L-lysine was the more effective precursor ( 30 times) for anabasine. 

In analogy with the biosynthesis of the Amaryllidaceae alkaloids (see Chapter 10) in which phenylalanine and tyrosine account for different... 

A group of indole alkaloids from Mesembryanthe-mum species. (-)-Mesembrine, [C17H23NO3, Mr 289.37, oil, bp. 186-190°C (40 Pa), [a)g -55.4° (CH3OH)] has a cocaine-like activity. The plants are used in South West Africa to prepare the drug Channa. Joubertiamine (C,3H, N02, Mr 245.32) occurs together with mesembrine. The biosynthesis of M. a. is similar to that of Amaryllidaceae alkaloids of the cri-nine group and proceeds from phenylalanine via cinnamic acid, p-coumaric acid, and 3-(4-hydroxy-phenyOpropanoic acid. The latter is then coupled with yV-methyltyramine. 

Most of the biosynthetic research done on Amaryllidaceae alkaloids was carried out in the 1960s and early 1970s. Since then, the only noteworthy study has been the biosynthesis of galanthamine (75) and related alkaloids (181). As in most alkaloid biosyntheses, that of the Amaryllidaceae follows a sequential pattern. 

Lycorine (1), the most frequent and characteristic of the Amaryllidaceae alkaloids, has been reported to be a powerful inhibitor of ascorbic acid (l-Asc) biosynthesis (436,437), and thus has proved to be a useful tool in studying Asc-dependent metabolic reactions in L-Asc-synthesizing organisms (438,439). Lycorine is actually a powerful inhibitor of the activity of L-galactono-y-lactone dehydrogenase, the terminal enzyme of l-Asc biosynthesis (440-443), which appears to be localized in the mitochondrial membrane (444,445). Galanthine (7) also has a high capacity to inhibit ascorbic acid biosynthesis (437). 

Keywords Amaryllidaceae alkaloid plant secondary metabolism alkaloid biosynthesis natural products systems biology galanthamine... 

Singh, A. and I. Desgagne-Penix, Biosynthesis of the Amaryllidaceae alkaloids. Plant Science Today, 2014. 1(2) p. 114-120. 

Medicinal Uses of Amaryllidaceae Alkaloids Mesembryanthemum and Sceletium Alkaloids Cephalotaxus and Homoerythrina Alkaloids Biosynthesis of Cephalotaxus Alkaloids Biosynthesis of Homoerythrina Alkaloids Systematic Value of Cephalotaxus and Homoerythrina Alkaloids... 

Biosynthesis of the third type of Amaryllidaceae alkaloids is represented by the formation of galanthamine (18) (Fig. 33.6). 

Studies on the biosynthesis of Amaryllidaceae alkaloids initiated as early as the 1960s. In 1957, Barton and Cohen proposed for the first time that norbelladine 2 or its congener alkaloid was probably the original precursor of other structurally diverse Amaryllidaceae alkaloids [103]. The primary metabolic processes leading to the Amaryllidaceae alkaloids include mainly (a) intramolecular phenol... 

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... 

Battersby AR, Binks R, Breuer SW, Fales HM, Wildman WC, Highet RJ (1964) Alkaloid biosynthesis. Part 111. Amaryllidaceae alkaloids the biosynthesis of lycorine and its relatives. J Chem Soc 1595-1609... 

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