Amaryllidaceae alkaloids plant family

C-Aromatic lycorine-type alkaloids have been discovered in the plants of the Amaryllidaceae family. Two new 2-oxo-pyrrolophenanthridinium alkaloids, zefbetaine (59) and zeflabetaine (60), together with several known Amaryllidaceae alkaloids, have been isolated from fresh mature seeds of Zephranthes flava by gradient solvent extraction, chromatography, and deri-vatization (108). Their structures were characterized by comprehensive spectroscopic methods, chemical transformations, and synthesis. They are listed in Fig. 9. 

Plant species belonging to the Amaryllidaceae family are widely distributed in several countries in the world. They are also cultivated as ornamental plants for their beautiful flowers and for the production of volatile oil. The study of Amaryllidaceae alkaloids began in 1877 with the isolation of lycorine [37, Fig. (9) and Table 2] from Narcissus pseudonarcissus [9], and the interest around this group of naturally occurring compounds has increased in time because of their effective antitumoral and antiviral activities. 

Amaryllidaceae alkalolda a group of alkaloids of complicated structure, found only in the plant family, Amaryllidaceae. They can be classified as phenylisoquinoline alkaloids (see Isoquinoline alkaloids), because their biosynthesis (Fig.) is similar to that of the isoquinoline alkaloids, beginning with phenylethylamine or tyramine and a carbonyl com-... 

Plants of the Amaryllidaceae family, including ca. 75 genera and about 1,100 species, are among the top 20 in the most widely considered medicinal plant families. A number of pharmacologically active compounds, such as phenols, alkaloids, lectins, peptides, etc., have been identified and characterized from this family. As primary constituents, up to 500 structurally diverse Amaryllidaceae... 

A unique characteristic for plants of the family Amaryllidaceae is the production of a group of structurally diverse but biogenetically relative alkaloids. Since lycorine 1 was isolated as the first alkaloid from Narcissus pseudonarcissus in 1877, up to 500 alkaloids have been identified from plants of this family to date. Furthermore, the number remains increasing every year. At present, most genera of this family are validated to produce Amaryllidaceae alkaloids. 

This type of Amaryllidaceae alkaloids owns an unique pyrrolo[t/,e]phenanthridine skeleton and is one of the most common alkaloids in plants of the family Amaryllidaceae (Table 17.3). Usually, they have a trans-junction in the B/C ring,... 

Alkaloids of this type belong to a newly established subgroup of Amaryllidaceae alkaloids and own a 10b,4a-ethanoiminodibenzo[( ,iflpyrane skeleton (Table 17.9). To date, a total of five alkaloids including four monomeric alkaloids 163-166 and one dimeric alkaloid 167 have been isolated from plants of the family Amaryllidaceae [41, 44]. 

Galanthamine-type alkaloids have a dibenzofuran nucleus and are the only group in the Amaryllidaceae alkaloids showing two ortho aromatic protons in ring A -(Table 17.11). Galanthamine 9 and lycoramine 192 are the two most abundant alkaloids in the family Amaryllidaceae plants, especially in the genera Galanthus and Narcissus. 

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... 

Several members of the Amaryllidaceae family of alkaloids display pronounced biological activities, and some Amaryllidaceae plants have played an important role in traditional herbal medicine for the treatment of various ailments. The most prominent examples of Amaryllidaceae alkaloids of biological relevance are narciclasine (55) and its congeners (pancratistatin and 7-deoxypancratistatin) and galantamine (62) (also commonly spelled galanthamine). These natural products also find application in modem medicine, and in this respect, pancratistatin is used in clinical... 

Although the alkaloids of the mesembrane type are structurally similar to certain alkaloids of the family Amaryllidaceae, they are generally found in the plants of the family Aizoaceae, but there have been several exceptions to this generalization. For example, amisine (580) has been isolated from Hymenocallis arenicola Northrop (57), and mesembrenol (581) has been isolated from Crinum oliganthum (41). The isolation of 580 and 581 represented the first instances in... 

As stated earlier, a wide range of compounds of different nature has been isolated from plant matrices using SFE however, the family of compounds more usually extracted by SFE has been alkaloids. Alkaloids of greatest interest for health and consumer reasons are caffeine (40) and nicotine (41), as well as purine alkaloids (42), cocaine (43) and indole alkaloids (44), which have been extracted using pure CO2. Meanwhile, C02-modified methanol has been used for the extraction of pirrolizidine alkaloids (45) and oxindole alkaloids (46). For the extraction of alkaloids from Amaryllidaceae... 

Most of the recent isolation studies have used fresh plant materials. Under these conditions the yield of crude alkaloids may approach 1% but usually is less than half of this value. When the crystalline alkaloid have been separated from each other and the amorphous fractions, an abundant alkaloid usually is present to the extent of 0.01% to 0.1%. At the other extreme, modem isolation techniques have made possible the isolation of pure alkaloids which represent only 0.0001% of the fresh plant weight. After conventional extractions of the ground plant material with an organic solvent, the basic fraction is transferred to an aqueous phase with dilute acid, and the nonbasic material is removed by extraction with an immiscible solvent. Considerable care must be exercised at this point since the hydrochlorides of the lactonic and nonhydroxylic alkaloids often are soluble in chloroform. Unlike the majority of alkaloids in the family, lycorine is practically insoluble in ethanol or chloroform and may be separated with ease from most alkaloid mixtures. Final isolation of pure alkaloids is achieved through differences in solubility, basicity, or adsorptivity on alumina. A method for the separation of the alkaloids by paper chromatography has been described (63a). Table 2 records the members of the Amaryllidaceae which have been examined for alkaloids up to November, 1958. Typical isolations are described below. 

More than sixty plants of the Amaryllidaceae have been examined for alkaloids in the past 6 years. Major contributions in isolation have been made by research groups in Germany, Sweden, Russia, Egypt, South Africa, and China. Exchange of alkaloid samples has not been frequent, and undoubtedly many of the alkaloids cited in Section IX will prove to be duplications. Typically a new alkaloid found in the family occurs in exceptionally minute amounts. Thus in laboratories not equipped with modern NMR- and mass spectrometers characterization often has been limited to simple physical constants, combustion analyses, and general comments about the IR- and UV-spectra. 

In the last group alone, there are more than 160 members, some of which are toxic. Many other alkaloids, some of great complexity, can be found in plants and frequently are referred to by the plant name. Thus, the Amaryllidaceae (exemplified by the common narcissus plant) alkaloids are a rich collection of complex stmctures. From the moss family Lycopodiaceae are obtained a group known as the Lycopodium alkaloids. Many miscellaneous alkaloids also are known. The book by Aniszewski is an excellent source of information on other types of alkaloids, their botanical distribution, and their biological and other features. 

Plants of the Amaryllidaceae family have been used for thousands of years as herbal remedies. The alkaloids from their extracts have been the object of active chemical investigation for nearly 200 years. Over the past two decades many have been isolated, screened for different biological activities, and synthesized by a number of research groups. An important handicap is the availability of these alkaloids, which are obtained only in minute quantities from natural sources. Since isolation in larger quantities is not praetieal, there is a strong case for the development of syntheses or semisyntheses of these alkaloids and their derivatives as potential prodrugs (35). 

It is well established that profiles of alkaloids vary with time, location, and developmental stage. In many instances, the site of biosynthesis is restricted to a single organ, but accumulation of the corresponding products can be detected in several other plant tissues. Long-distance transport must take place in these instances. There are only a few data on the ontogenic variations and distribution of alkaloids in species of the Amaryllidaceae family, and some results have been obtained in Narcissus species, such as N. assoanus (with only lycorine-type alkaloids) or N. confusus (with alkaloids of the homolycorine, hemanthamine, tazettine, and galanthamine types) 84,87). 

Haemanthamine and haemanthidine A P dissipation, cell cycle arrest with increased pl6 expression and Chkl Ser345 phosphoiylation Human leukemic Juikat cells Alkaloids isolated from plants of Amaryllidaceae family. Haemanthidine is more active that haemanthamine as apoptotic inductor. [134]... 

Alkaloids are found most commonly in dicotyledonous angiosperms and are uncommon in algae, bryophytes, ferns, and monocotyledonous angiosperms. However, alkaloids are known from the lower plant Lycopodium, and from the monocotyledonous families Amaryllidaceae, Dioscoreaceae, Liliaceae, Orchidaceae, and Poaceae. Alkaloids are not common in gymnosperms, although they are encountered in several conifers and occasionally in other gymnospermous groups. 

The crinine- and haemanthamine-type alkaloids, together with lycorine-type alkaloids, are the most abundant alkaloids in the plants of the family Amaryllidaceae. Both crinine-type and haemanthamine-type alkaloids have a 5,10b-ethano bridge moiety in their frameworks, a very significant taxonomic feature, and the configurations of the 5,10b-ethano bridge are opposite to each other (Table 17.5). Scarcely, haemanthamine-type alkaloids bujeine 132 owns an unusually modified bridge with a heteroatom between Cll and C12 and an acetoxymethyl substituent at the 11-endo position [39]. 

Alkaloids of this type belong to another new subgroup isolated from the Amaryllidaceae family plants and own a 7-arylindole or 7-aryl-2,3-dihydroindole skeleton (Table 17.10). It is interesting that alkaloids of this type 171-174 recently isolated from the genus Narcissus cultivar show a rare axial chirality [45]. 

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). 

A widespread alkaloid family is made up of phenylalanine-tyrosine derivatives. These amino acids are precursors of a variety of compounds alkaloids, flower pigments, phenylpropane acids, lignins, etc. In most cases, deamination is the first reaction, but sometimes decarboxylation, O-methylation, or A-methylation occurs. The resultant protoalkaloids can be transformed into an impressive number of alkaloids. In closely related orders, e.g., Ranales, Berberidales, Aristolochiales, and Rhoeadales, the commonly synthesized compound is norlaudanosoline, and it acts as a precursor for all alkaloids in these plants. In some orders such as Aristolochiales, the alkaloids can be converted into compounds that do not give an alkaloid-positive reaction. Another group of plants with tyrosine- and phenylalanine-derived alkaloids are the Amaryllidaceae and related taxa. 

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