Narcissus and Daffodil

410 J.R. Murray
to certain RNA viruses, which contain glycoproteins with mannose linkages,
including Human Immunodeficiency Virus (HIV) and Human T lympho-tropic
Virus (HTLV), either as a therapy or as a diagnostic (Forrest et al., 1991).
In addition, the use of bulb extract with vinegar has been claimed for the treatment
of fungal diseases of the skin, in particular, tinea pedis (Sugimoto, 1994).
Topical treatments derived from hot-water extracts of ground daffodil bulbs are
claimed to dilate peripheral veins, improve blood flow to improve metabolism and
thus complexion, and also to prevent skin ageing and damage to skin by ultraviolet
light (Kobayashi, 1982).
PATENTS RELATED TO GALANTHAMINE
Galanthamine patents fall into four groups – production, formulation and use
patents and galanthamine analogues. The parent molecule has been well categorised
many years ago, so compound patents on the molecule itself do not feature in
the literature. However, compound patents around analogues and derivatives of
galanthamine and precursors of galanthine do.
Production patents
Introduction
Galanthamine was first extracted from members of the snowdrop family (hence
galanthamine from the genus Galanthus). Commercially, daffodil bulbs are far
more appropriate, as they are available in bulk supplies. Extraction from daffodils
in the UK has been particularly relevant, as some 70% of the world’s supply of daffodil
bulbs come from the British Isles, with growers in the east of England playing
a major role. Handling large volumes of bulbs has its problems. McFarlan Smith
(Meconic Ltd.) in Edinburgh now has one of the largest plant extraction units in
Europe dedicated to galanthamine extraction.
Clearly with bulb production being rather a slow process, the extraction method
does lack some flexibility, and much effort has been put into exploring methods of
synthetic production. Unfortunately, the galanthamine molecule has three chiral
centres with eight possible enantiomers. In practice, one of these centres is effectively
‘locked’ and thus four stereoisomers are possible. However, the plant produces
only one stereoisomer, the (–)-galanthamine, and it is this isomer that is most
active pharmacologically. Synthetic production problems lie in producing the one
active isomer and in overcoming a crucial oxidative phenyl-coupling step that has
a particularly low yield.
Extraction patents
Given that extraction technologies contain as much art as science, it is not surprising
that only a few patents exist around this method of production. However, such
patents do exist, particularly from Eastern European authors, with the starting
material sometimes involving sources other than daffodils. For example, the roots