Alkaloids Amaryllidaceae family

The most important alkaloid containing families are the Amaryllidaceae, Apocynaceae, Asteraceae (Eupatorieae, Se-necioneae), Boraginaceae, Euphorbiaceae, Fabaceae, Laur-aceae, Liliaceae, Loganiaceae, Menispermaceae, Papavera-ceae, Ranunculaceae, Rubiaceae, Rutaceae, and Solanaceae (Cordell, 1978 Dalton, 1991). 

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 

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]. 

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. 

Despite the great importance of some members of the Amaryllidaceae family of alkaloids, only limited information on the subsequent steps of their biosynthesis is available to date. However, in analogy to other classes of secondary metabolites presented within this chapter, the diversity of 4 -0-methylnorbelladine (65)-derived natural products can easily be explained by means of different oxidative phenolic 

Although tazettine (62) is one of the most widely reported alkaloids in the Amaryllidaceae family, it was found to be an extraction artifact from pretazettine (64) (75). 

The variety of structural types that are encountered in alkaloids belonging to the Amaryllidaceae family can be conveniendy classified, from the point of view of their basic skeleton, along the following lines (see Figure 1)  

The Ley research group [76] developed a flow process for the multistep synthesis of ( )-oxomaritidine, an alkaloid found in the Amaryllidaceae family, known to have antineoplastic activity (Scheme 34) [77, 78]. The route does not involve intermediate purification of the products, which is necessary in the previously reported 

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 

Iminium ion-vinylsilane cyclizations closely related to the one described here have been used to prepare indolizidine alkaloids of the pumiliotoxin A and elaeokanine families, indole alkaloids, amaryllidaceae alkaloids, and the antibiotic (+)-streptazolin. The ability of the silicon substituent to control the position, and in some cases stereochemistry, of the unsaturation in the product heterocycle was a key feature of each of these syntheses. 

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. 

Tazettine (62) is a widely reported alkaloid in the Amaryllidaceae family, particularly in Narcissus (see Tables VIII and IX), although it is known to be an extraction artifact of pretazettine (64) (75). All the alkaloids of the tazettine type that are isolated from Narcissus species show the typical methylenedioxy group between the C-8 and C-9 positions. Obesine (67) is an exceptional tazettine-type alkaloid with a seven-membered ring 76). 

Intramolecular ene reactions of acylnitroso compounds have been studied extensively32 and used in the synthesis of alkaloids of the Amaryllidaceae family. In these cases the only-stereochemical control observed was in the cyclization to form r/s-fused bicyclo[4.3.0] systems 133,34 

Chapter 3 by S. Prabhakar and M.R. Tavares summarizes recent advances in the synthesis of Amaryllidaceae alkaloids, an important class of naturally-occurring bases and neutral compounds. The increased activity in the synthesis of these alkaloids over the last decade is undoubtedly due to the fact that certain members of this family possess interesting and useful biological properties. Many elegant syntheses, chiral and otherwise, of structures incorporating many asymmetric centres are reviewed. 

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] 

The synthesis of 1-arylcyclopropylimines has been improved (34), and their conversion to A - or A -pyrrolines for further elaboration wiA methyl vinyl ketone and methyl vinyl ketone analogs has been brilliantly employed by Stevens and his co-workers for eflScient syntheses of not only Sceletium alkaloids and the structurally related alkaloids of the Amaryllidaceae family, but alkaloids of diverse structure representing other alkaloid families (46). 

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