Narcissus and Daffodil

Galanthamine extraction 269
To obtain greater amounts of degradation products the experiment was repeated
with 10% sulphuric acid at 70 °C. The components of the resulting solution were
separated by preparative HPLC.
It was found that the excessive use of sulphuric acid led to an epimerisation of
galanthamine (1) at the C3-atom and the formation of epigalanthamine (4). This
should be taken into consideration when literature reporting the isolation of
epigalanthamine from plant material is found. Another compound isolated from
the reaction mixture was 3,4-anhydro-galanthamine (3). The compound was not
stable over a three week period. The formation of a second aromatic unit derived
from galanthamine was found in the nuclear magnetic resonance (NMR) spectrum
of a third degradation product which was isolated. This can occur only if a
rearrangement in the galanthamine molecule takes place. A similar reaction is
known after treatment of morphine with acid (apomorphine rearrangement).
However, the methyl ether bond of galanthamine was not broken by sulphuric
acid. The resulting molecule was identified as 6-O-methyl-apogalanthamine (5).
The scheme on the following page shows the probable mechanism of the apogalanthamine
rearrangement which leads to the formation of 6-O-methyl-apogalanthamine.
CONCLUSIONS
Thirty commercially available species and cultivars from the Amaryllidaceae family
were tested for their galanthamine content. Several large-cupped daffodil cultivars
were found to be rich in galanthamine, in particular Narcissus ‘Carlton’, which is
cultivated on a large scale in the Netherlands and the UK. This cultivar proved to
be a suitable subject for further studies on a potential galanthamine extraction. In
this cultivar galanthamine was found to be present in all parts of the plant. The
highest content was found in the bulb, which is convenient for technical extraction.
Galanthamine concentration in the plant fluctuated strongly during the year.
The best time for harvesting the bulbs would be a short time after the usual lifting
period in the Netherlands. The content of galanthamine in bulbs could be
increased by applying fertilisers.
For isolation of galanthamine on a technical scale the following procedure is recommended.
The bulbs are thoroughly homogenised with dry sodium carbonate
and extracted with petroleum spirit (which is cheaper than n-pentane, n-hexane
or n-heptane). The organic phase is concentrated by evaporation and extracted
with diluted sulphuric acid. The acidic phase is adjusted to pH 5.0 with ammonia
solution immediately after extraction, and separated from accompanying substances
by extraction with diethyl ether. The aqueous phase is adjusted to pH 9.0
and extracted again with diethyl ether. The ether extract is dried and dissolved in
warm isopropanol. Crude galanthamine base crystallises during cooling, using a
seed crystal if necessary. Pure galanthamine is obtained by re-crystallisation of the
crude product from isopropanol. Galanthamine remaining in the mother liquids
of the crystallisations is obtained after evaporating the remaining solution in
isopropanol, dissolving the residue in acetone and precipitation with ethanolic
hydrogen bromide solution. The procedure is simple, relatively fast and consists of