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VetBooks.ir Chapter 66

Toxicity of Yew (Taxus spp.) Alkaloids

Christina R. Wilson and Stephen B. Hooser

INTRODUCTION by Marme ´, a French scientist (Hilger and Brande, 1890).
However, it was not until 1956 that Graf and Boeddeker dis-
Yews (Taxus spp., Taxaceae) are evergreen plants often used
covered that taxine was a mixture of heterogeneous com-
for ornamental landscaping in many areas of the United
pounds. Further investigations using electrophoretic analyses
States, Europe, and elsewhere throughout the world.
of taxine extracts revealed two major bands, thus recognizing
Common varieties in the United States are English yew
the presence of two major types of taxine alkaloids: taxine A
(Taxus baccata), American yew (Taxus canadensis), Japanese
and taxine B (Graf, 1956). The farthest migrating electropho-
yew (Taxus cuspidata), and Pacific or Western yew (Taxus retic band was designated taxine A, which comprised approx-
brevifolia)(Kingsbury, 1964). These plants can be highly
imately 1.3% of the total alkaloid extract. The other
toxic and have been implicated in numerous human and ani-
electrophoretic band, taxine B, represented approximately
mal poisonings. The poisonous taxine alkaloids are present in
30% of the total alkaloid fraction extracted from T. baccata
the foliage, bark, and seeds of the plants but not in the fleshy
L. (Graf, 1956; Graf and Bertholdt, 1957). Subsequent analy-
scarlet aril (berry) (Bryan-Brown, 1932; Kingsbury, 1964).
ses elucidated the molecular and structural formula of taxine
A as well as its basic physical and chemical properties (Graf
and Bertholdt, 1957; Graf et al., 1982). A structural analog of
Historical Background
taxine A, 2-deacetyltaxine A (C 33 H 45 NO 9 ), was isolated from
References to yew toxicity date back more than two mil- the leaves of T. baccata in 1994 (Poupat et al., 1994). The
lennia (Bryan-Brown, 1932). In the first century BCE, chemical and structural properties of taxine A and 2-
Julius Caesar (102 44 BCE) wrote of Catuvolcus, the deacetyltaxine A are given in Table 66.1 and Fig. 66.1.
king of Eburones, who poisoned himself with yew “juice” Although the preliminary structure of taxine B was first
(Fro ¨hne and Pfa ¨nder, 1984). Ancient Celts often commit- reported in 1986 (Graf et al., 1986), the molecular and struc-
ted ritual suicides by drinking extracts from yew plants tural formulas were not completely elucidated until 1991
and applied the poisonous sap to the tips of their arrows (Ettouati et al., 1991). Purified taxine fractions from various
during the Gaelic Wars (Foster and Duke, 1990; Hartzell, Taxus spp. revealed the presence of several taxine B-related
1995). Some primitive cultures are reported to have used compounds. Isotaxine B (C 33 H 45 NO 8 ), a structural isomer of
yew extracts as hunting and fishing aids (Watt and taxine B, is present as a major constituent in the alkaloid frac-
Breyer-Brandwijk, 1962; Hartzell, 1995). During the 18th tions (Poupat et al., 1994; Jenniskens et al., 1996; Potier et al.,
and 19th centuries, concoctions brewed from yew leaves 1997; Adeline et al., 1997). Present as minor constituents in
were documented as having been used as an abortifacient Taxus spp. are 1-deoxytaxine B and 1-deoxyisotaxine B
or an emmenagogue by women in Europe and India (Fig. 66.2)(Jenniskens et al., 1996; Potier et al., 1997). The
(Bryan-Brown, 1932; Watt and Breyer-Brandwijk, 1962). physical properties and chemical structures for taxine B
and isoforms of taxine B are detailed in Table 66.1 and
Fig. 66.2. Other minor constituents, comprising approxi-
Chemical Characterization
mately 2% of the total concentration, are the taxine B pseu-
The first preparation of an amorphous, white, noncrystalline doalkaloids 13-deoxo-13α-acetyloxytaxine B (C 35 H 49 NO 9 ),
powder called “taxine” originated from an analysis of alkaloid 13-deoxo-13α-acetyloxy-1-deoxytaxine B (C 35 H 49 NO 8 ), and
content from yew foliage (T. baccata L.) in 1856 by Lucas. It 13-deoxo-13α-acetyloxy-1-deoxy-nortaxine B (C 34 H 47 NO 8 )
was isolated in crystalline form approximately 20 years later (Appendino et al., 1997).

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