Hemanthamine

Protein biosynthesis is essential for all cells and thus provides another important target. Indeed, a number of alkaloids have been detected (although not too many have been studied in this context) which inhibit protein biosynthesis in vitro. Emetine from Cephaelis ipecacuanha (Rubiaceae) is the most potent plant constituent other alkaloids with the same ability include harringtonine, homoharringtonine, cryptopleurine, tubulosine, hemanthamine, lycorine, narciclasine, pretazettine, pseudolycorine, tylocrepine, and tylopherine [5] and furthermore, ajmaline, berberine, boldine, cinchonine, cinchonidine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, salsoline, sanguinarine,... 

The large number of structurally diverse Amaryllidaceae alkaloids are classified mainly into nine skeleton types, for which the representative alkaloids are norbelladine, lycorine, homolycorine, crinine, hemanthamine, narciclasine, tazettine, montanine, and galanthamine (Fig. 1). With the aim of unifying the numbering system of the different skeleton types, Ghosal s model will be used in this review (20). 

The montanine-type alkaloids, also deriving from the hemanthamine series, are very unusual. Only two, namely pancracine (73) and nangustine (74), have been isolated from two species, both belonging to the Narcissus section of this genus. Nangustine has a unique substitution pattern (80), being the first 5,11-methanomorphanthridine alkaloid with a C-3/C-4 substitution, instead of a typical C-2/C-3. 

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). 

Skeleton types LY, lycorine FIL, homolycorine HT, hemanthamine TZ, tazettine NC, narcielasine MN, montanine GA, galanthamine OA, other alkaloids. Alkaloid names see Tables I-VII. 

Crinine, Hemanthamine, Tazettine, Narciclasine, and Montanine Types... 

This group includes the alkaloids derived from 5,10b-ethanophenanthridine (crinine and hemanthamine types), 2-benzopyrano[3,4-c]indole (tazettine type), phenanthridine (narciclasine type), and 5,11-methanomorphanthridine (montanine type) skeletons, originating from a para-para phenol oxidative coupling (Fig. 8). 

The alkaloid ismine (72) has also been shown (206) to be a transformation product of the crinine-hemanthamine series. The precursor, oxocrinine labeled with tritium in the positions 2 and 4, was administered to Sprekelia formosissima plants and the radioactive ismine (72) isolated was shown to be specifically labeled at the expected positions. 

Figure 10. Proposed biosynthetic pathways to hemanthamine (53) and montanine (98).

The presence of an A -methyl group (2.4-2.5 ppm) in tazettine-type alkaloids immediately distinguishes them from the hemanthamine type, from which they proceed biosynthetically. Moreover, the H NMR spectrum always shows the signal corresponding to the methylenedioxy group. 

Like lycorine (1), hemanthidine (55) has stronger analgesic and anti-inflammatory activity than aspirin (489,496), and vittatine has been found to potentiate the analgesic effect of morphine (60). Moreover, some alkaloids of this series, such as hemanthamine (53) or papiramine (48) have a hypotensive effect (41,498), and hemanthamine shows strong antiretroviral activity (483). 

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