Narcissus and Daffodil

244 O.A. Cherkasov and O.N. Tolkachev
A number of galanthamine derivatives have been obtained. A study of structure–activity
relationships revealed potent N-methyl-galanthamine hydroxide,
which is more than 20 times as active as galanthamine in anticholinesterase activity
(Abdusamatov, 1968, 1972). Three-dimentional quantitative structure–activity
relationship studies of galanthamine and its analogues have been carried out.
From the calculation of the lowest energy conformations, it was shown that the
dominant factor was the steric effect, whereas the electrostatic effect of the large
substituent decreased activity (Luo et al., 1995).
SOURCES OF GALANTHAMINE AND LYCORINE USED IN MEDICINE
Galanthamine and lycorine have so far attracted most interest for their medical
applications. Galanthamine was isolated for the first time from Galanthus woronowii
Losinsk. by Proskurnina and Yakovleva (1952, 1955), and was afterwards found in
many other species of Amaryllidaceae, including Leucojum aestivum L., Ungernia
victoris Vved. and Pancratium and Sternbergia species (Abdusamatov, 1972; Boit,
1961; Cherkasov, 1975, 1976, 1977; Cherkasov et al., 1984a,b, 1985, 1986, 1988,
1989; Cherkasov and Tolkachev, 1996; Gorbunova et al., 1978; Maisuradze et al.,
1984, 1985; Sadykov and Khodzhimatov, 1988). On a commercial scale, galanthamine
has been produced from Galanthus nivalis L. in Bulgaria under the name
‘Nivalin’. In the former Soviet Union galanthamine was produced from leaves of
G. woronowii in Russia and from leaves of Ungernia victoris in Uzbekistan (Abdusamatov,
1968, 1972; Cherkasov et al., 1984a; Khamidkhodzhaev, 1967, 1977, 1982).
U. victoris is an endemic plant growing widely in Tajikistan in the Gissar mountain
region, the natural area of which is limited (Cherkasov et al., 1984a). Leaves of the
plant contain 0.05–0.15% galanthamine, while its content in bulbs varies from
0.05% up to 0.40–0.60% in some populations. The limited supply of U. victoris has
been exhausted by commercial harvesting. Attempts at the cultivation of Ungernia
were unsuccessful because of its slow regeneration: it would require about 45–50
years to restore the former production from small bulbs or from seeds. As the natural
supply of the plant material does not satisfy the total demands of the pharmaceutical
industry, a search for alternative natural sources of galanthamine is of
great importance (Cherkasov, 1977; Cherkasov et al., 1984a; Khamidkhodzhaev,
1967, 1984).
Measurement of the galanthamine levels in Amaryllidaceae has been carried out
by a number of groups in Russia (e.g., Patudin et al., 1978; Gorbunova et al., 1978;
Sadykov and Khodzhimatov, 1988). The concentration of galanthamine in
Amaryllidaceae has been found to vary widely between the species from the 18
genera studied, from trace amounts to 0.5%. In Leucojum vernum, Galanthus elwesii,
G. nivalis, Ungernia victoris and Narcissus, galanthamine was found to be the principal
component of the alkaloid fraction, making up from 30 to 50% of the alkaloid
fraction and corresponding to 0.05–0.5% on a dry weight basis (Cherkasov, 1975;
Gizba et al., 1982).
Galanthamine is usually accompanied by lycorine in plants. Lycorine has been
isolated from various species of the Amaryllidaceae family, including Amaryllis
belladonna var. purpurea, Cooperanthes (Cooperia × Zaphyranthes) hortensis, Crinum
defixum, C. laurentii, C. powelliti var. krelagei, C. yemense (latifolium), Eustephia yuyuensis,