Narcissus and Daffodil

282 R.M. Moraes
years, a yield of 18 t/ha (Langton and Hanks, 1993). This would be a more suitable
growing system for a high galanthamine content cultivar which was expensive,
and in short supply. An area of 7164 ha would be needed to equal the previous
production of galanthamine for a two-year drug supply to treat 30% of the US
Alzheimer patients using high yielding cultivars such as Narcissus ‘Inglescombe’
(174 mg per 100 g of dry weight at bulb dormant stage). Cultivation of high yielding
bulbs would decrease all production requirements and costs (plantation size,
handling, storage, extraction and waste products). Furthermore, harvesting
‘Inglescombe’ during active growth (284 mg per 100 g dry weight) would yield
63% more galanthamine than dormant bulbs and would decrease costs even more.
Another strategy to reduce the cultivation area would be the semi-synthetic
approach, extracting galanthamine analogues (lycoramine, demethyl-lycoramine,
narwedine and demethylnarwedine) and chemically converting these to galanthamine.
Following the first promising results of galanthamine in clinical trials,
many semi-synthetic derivatives of galanthamine were synthesised. A series of
carbamates of 6-demethylgalanthamine were found 1000 times more potent than
galanthamine as cholinesterase inhibitors (Bores and Kosley, 1996). Several esters
were also prepared and among these, the adamantyl ester (2) is the most promising
derivative. In addition, the adamantyl ester has greater selectivity and a better
oral pharmacokinetic profile, and thus a higher oral therapeutic index, compared
with galanthamine.
The economically viable production of galanthamine, directly or by semisynthesis
from natural resources for pharmaceutical purposes, calls for the co-ordinated
contribution of many scientists in a multidisciplinary effort. Treatment of
AD patients with galanthamine will require the production of large quantities of
narcissus biomass of high galanthamine content. Substantial research is needed to
define the most favourable agronomic practices and to optimise extraction and
isolation of the pure compound.
ACKNOWLEDGEMENTS
Special thanks are due to James D. McChesney for his support and guidance
during this research on galanthamine production from narcissus. My gratitude to
the dedication and views of my collegues and collaborators on our galanthamine
work, Jairo K. Bastos, Charles L. Burandt Jr., Julie Mikell, N.P. Dhammika
Nanayakkara and Thomas Sharpe. I am especially indebted to Joseph Atkins,
Allison Best, Camilo Canel, Hala ElSohly, Jeffrey Krans and Larry Walker for
their helpful discussions on this chapter. Thanks to my sons Cesar, Marcos and
my mother Maria Martha for their love.
This chapter is dedicated to the memory of my loving father and great
agronomist Leo Gomes de Moraes.
REFERENCES
Anderson, L. (1989) Daffodils. American Horticulturist, 68 (2), 21–23.
Anon. (1999) Statistiek voorjaarsgewassen. Bloembollencultuur, 110 (6) (BC Centraal supplement),
1–4.