Taxane alkaloids

The anticancer drug taxol is produced by endophytes from Taxus brevifolia (Stierle et al., 1993). An isolated occurrence of the taxan alkaloids has been reported from Corylus avellana (Betulaceae), which is not associated with an endophyte (although the pathway genes might have been imported by an endophyte at an earlier stage) (Ottaggio et al., 2008). Podophyllotoxin is produced by endophytes of Podophyllum peltatum (Eyberger et al, 2006). 

Taxane alkaloids have a very limited distribution within the plant kingdom, and occur only in two genera of the yew family (Taxus and Austrotaxus). The genus Austrotaxus is monotypic (A. spicata Compt), but contusion exists on the systematics of the genus Taxus, especially as regards the taxonomic status of certain Asian yews. Reference will be given here to the Krttssmann classification (Table 1) [28]. 

Early separation methods, based on the selective partition of crude taxine between an organic solvent and water solutions of different pH values [31] have been abandoned, and column chromatography on silica gel using mixtures of CHClj-EtOH as eluant is today the method of choice. Further purification can be achieved on TLC or with HPLC. Unlike crude taxine, taxane alkaloids are often crystalline compounds, especially those of the taxine A-type. 

Taxane alkaloids are made up of a terpenoid core and a phenylpropanoid (3-amino acid, joined by an ester bond. They can be classified according to the carbon-carbon connectivity of the terpenoid core and the type of the side-chain. Thus, the diterpenoid core can be of the taxane- (Tables 3-8), 11 (151 )abeotaxane-(Table 10), 2(3->20)abeotaxane-(Table 2) or 3-11-cyclotaxane (Table 9) type, whereas the side chain can be Winterstein s add [L(R) (3-dimethylamino-P-phenylpropionic add] or N, A/-dimethylphenylisoserine (2R, 3S (threo) a-hydroxy-3-dimethylamino-P-phenylpropionic acid). Further modification occurs in the... 

A few main subclasses can accommodate most alkaloids, and a system of nomenclature based on names defined in the literature can avoid the confusing use of very similar trivial names that plague the literature on taxoids. Thus, taxine B is a taxane alkaloid [24], whereas taxin B is a non-nitrogenous 2(3->20)abeotaxane [33]. 

The thirty-seven Taxus alkaloids isolated through July 1995 are reported in Tables 2-10, along with their botanical source [species, plant part (I - leaves b = bark, r = roots)]. A. spicata Compt is the richest source of taxane alkaloids, in terms of chemical diversity, and 2 -deacetoxyaustrospicatine (4f) is the most widespread alkaloid (three Taxus species and A. spicala). The various taxane alkaloids can be divided into the following structural types ... 

Spicaledonine-type (Table 9, 8a,b) these alkaloids are the 3,11-cycloderivatives of taxane alkaloids of the 13-oxo-type (taxine B and comptonine types). 

Two taxane alkaloids have been investigated by diffraction techniques taxine A (la) [23] and 2 deacetoxyaustrospicatine (41) [49], The results gave important information on the orientation of the side chain relatively to the terpenoid core. In both cases the aromatic ring is close to the terpenoid core, but in 4f the phenyl and the catbonyl are antiperiplanar, whereas in taxine A they are synclinal (cf. C and A in Scheme 3). As a result, the protons closer to the phenyl ring are H(6a) in taxine A and H(14a) in 4f. This is in accordance with the results of the H-NMR analysis [46], In 4f, the conformation with C-l and the phenyl antiperiplanar is stabilized by hydrophobic interactions with the methyl of the 13-acetate [49], The X-ray features of the terpenoid core of 4f and taxine A show linear strain at several carbon-carbon bonds, as generally observed in taxoids [55]. 

Taxanes are found only in the gymnospermous family, the Taxaceae. Taxane alkaloids (derived from these ter-penes) are responsible for the extremely poisonous properties of the genus Taxus (Fig. 22.5). 

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