Content
Various types of alkaloid structure are encountered
in the daffodil family, the Amaryllidaceae, and
they can be rationalized better through biosynthesis
than by structural type. The alkaloids arise
by alternative modes of oxidative coupling of
precursors related to norbelladine (Figure 69),
which is formed through combination of 3,4-
dihydroxybenzaldehyde with tyramine, these two
preursors arising from phenylalanine and tyrosine
respectively. Three structural types of alkaloid
can be related to 4*-O-methylnorbelladine by
different alignments of the phenol rings, allowing
coupling para–ortho (A), para–para (B), or
ortho–para (C) as shown in Figure 69. For
galanthamine, the dienone formed via oxidative
coupling (C) undergoes nucleophilic addition from
the phenol group, forming an ether linkage (compare opium alkaloids, page 328), and the
sequence is completed by reduction and methylation
reactions. For lycorine and crinine, although details
are not given in Figure 69, it is apparent that
the nitrogen atom acts as a nucleophile towards
the dienone system in a similar manner, generating
the new heterocyclic ring systems. Alkaloids such
as lycorine, crinine, and galanthamine can undergo
further modifications, which include ring cleavage
reactions, generating many more variations than
can be considered here.
|
The Amaryllidaceae family
includes Amaryllis, Narcissus, and Galanthus,
and the alkaloid content of bulbs from most
members makes these toxic. Lycorine was first
isolated from Lycorus radiata, but is common
and found throughout the family.
Galanthaminefrom snowdrops (Galanthus species) is currently
an important drug material of value in treating
Alzheimer’s disease.
 |
| Figure 69 |
Galanthamine
Galantamine (galanthamine) can be isolated from a number of species of the Amaryllidaceae,
including snowdrops (Galanthus species), daffodils (Narcissus pseudonarcissus), and
snowflakes (Leucojum species), where typical content varies from about 0.05 to 0.2% in
the bulbs. It is currently isolated for drug use from the bulbs of wild Leucojum aestivum
and Galanthus species, since commercial synthesis is not economic. Galantamine acts as
a competitive cholinesterase inhibitor, and enhances cognitive function in the treatment of
Alzheimer's disease by raising acetylcholine levels in brain areas lacking cholinergic neurones.
In common with other treatments for Alzheimer's disease, it does not cure the condition, but
merely slows the rate of cognitive decline
|