Narcissus and Daffodil

274 R.M. Moraes
(Katz and Taneck, 1993) and nicotine (Moormann and Werner, 1997) and alcohol
dependence (Opitz, 1996). Approval for the treatment of AD, together with its
current uses, will create a strong and stable demand for galanthamine, even
though other competitive anticholinesterase drugs are available. Recent estimates
of the retail price of galanthamine are approximately US$50 000 per kilogram
(Shieh and Carlson, 1994). Under present conditions, the projected demand for
galanthamine would not be met by the current supply without significantly
increasing its price. Most commercially available galanthamine is extracted from
wild-harvested Leucojum aestivum in Bulgaria and Russia (Poulev et al., 1993).
Research on the chemical synthesis of galanthamine has been aimed at total
synthesis and also at the creation of more potent derivatives to minimise the
dependence on natural resources (Bores and Kosley, 1996). Han et al. (1992) and
Kosley et al. (1998) have prepared series of semi-synthetic derivatives. The adamantyl
ester (2) is the most promising compound due to better affinity, selectivity
for acetylcholinesterase and more favourable pharmacokinetics, thus reducing
the amount of drug required to treat each AD patient. Research on total synthesis
has improved galanthamine yields. However, the yield is still considered moderate
(45 to 50%) and too low for economical commercial application (Czollner et al., 1998;
Eichhorn et al., 1998).
O
O
6
O
Adamantyl-ester galanthamine, 2
In addition to galanthamine, there is great interest in several other Amaryllidaceae
alkaloids due to their wide range of biological activities, including antiviral, antimalarial
and anticancer properties (Gabrielsen et al., 1992; Likhiywitayawuid et al.,
1993). Pretazettine (11) is a highly cytotoxic compound against human lymphoid
neoplasm. It has also been used in combination with DNA-binding alkylating agents
in the treatment of the Rauscher leukaemia virus (Furusawa et al., 1978). Narciclasine
(9) has anticancer, antimitotic and antiviral activity (Evidente et al., 1986; Pettit et al.,
1990). Lycorine (6) and lycoricidine possess plant growth-inhibiting properties and
antiviral activity (Ieven et al., 1983). According to Jimenez et al. (1976), dihydrolycorine,
haemanthamine (7), lycorine, narciclasine and pretazettine are protein inhibitors
in eukaryotic organisms due to their binding to the 60S ribosomal subunit.
Lycorine inhibits translation at the termination step (Vrijsen et al., 1985).
3
N
OH
1
2