Taxus brevifolia taxol from

Nature has been a potential source of therapeutic agents for thousands of years. An impressive number of modem dmgs have been derived from natural sources. Over the last century, a number of top selling dmgs have been developed from natural products. Anticancer dmg vincristine from Vinca rosea, narcotic analgesic morphine from Papaver somniferum, antimalarial dmg artemisinin from Artemisia annua, anticancer dmg Taxol from Taxus brevifolia and antibiotic peniciUins from Penicillium ssp. are just a few examples. 

Taxus (yew) trees contain alkaloids called taxanes that have anticancer activity and are the basis of the semisynthetic anticancer drugs paclitaxel and docetaxel (see separate monographs), which are based on taxol, from Taxus brevifolia. 

The most enthusiastic reports concern the diterpenoids paclitaxel, Taxol (from Taxus brevifolia) and docetaxel, Taxotere (from Taxus baccata) having unique tri- or tetracyclic 20 carbon skeletons extracted from the bark of yew. This tree was known as a toxic plant for animals and humans for centuries. Monroe E. Wall and Mansukh C. Wani, at the Research Triangle Park (Chapel Hill, USA), identified the active principle of the yew tree in 1971. In 1979, Susan Horwitz of the Department of Molecular Pharmacology, Albert Einstein College of Medicine (New York) suggested that paclitaxel s mechanism of action was different from that of any previously known cytotoxic agent. She observed an increase in the mitotic index of P388 cells and an inhibition of human HeLa and mouse fibroblast cells in the G2 and M phases of the cell cycle. 

Among other antineoplastic agents of plant origin, the narcissus alkaloid pseudolycorine (22) is active against Rauscher leukemia.136 Taxol, from Taxus brevifolia, is active against a number of experimental neoplastic systems its structure (23) was reported.The sesquiterpene lac-tonesl38,139 and bufadienolidesl are cytotoxic. 

Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971 93 2325-7. 

A fine example of such a semi-synthesis is the preparation of the anti-cancer drug paclitaxel (Taxol ), a relatively scarce compound from Taxus brevifolia. Here, the natural and better accessible 10-deacetylbaccatin III, isolated from the leaves of Taxus baccata, provides the complicated ring system of paclitaxel, including all substituents with the right stereostructure (Scheme 5.1). In just four reaction steps [5] paclitaxel is obtained from 10-deacetylbaccatin III. 

Taxol (1), Fig (6), is another important diterpene with anticancer properties. It was isolated in 1971 from Taxus brevifolia Nutt. (Taxaceae), which is a slow growing shrub/tree, found in the forests of N.W Canada and USA. Taxol is one of over one hundred taxanes, which have been... 

With an increasing number of novel lead candidates that enter into preclinical development, considerable resources are needed to identify impurities. LC/MS-based approaches provide integrated sample cleanup and structure analysis procedures for the rapid analysis of impurities. This advantage was demonstrated during the preclinical development of TAXOL . LC/MS played an important role for the identification of impurities contained in extracts and process intermediates from Taxus brevifolia and T. baccata biomass. Because drugs derived from natural sources often have a very diverse set of structural analogs, it is important to determine which... 

Taxol, a material occurring in nature, and extracted from Taxus brevifolia (i.e. the Pacific yew tree). It consists of the A, B and C variants. Taxol is not water soluble, thereby complicating its delivery in vivo for therapeutic purposes. 

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). 

Paclitaxel (Taxol Bristol Myers Squibb 14) and its semisynthetic analog docetaxel (15) are two of the most important anticancer agents of the last 25 years. Paclitaxel was isolated originally by Wall and Wani from Taxus brevifolia (23) and named taxol this name was later trademarked by Bristol-Myers... 

Taxol is a natural product isolated in very low yield from Taxus brevifolia and is used in the treatment of cancer (110). The extreme chemical complexity of Taxol makes production by total synthesis uneconomical. However, a semisynthetic approach using the naturally derived 10-deacetylbaccatin III (66) condensation with iST-benzoyl-(2J2, 3S)-3-phe-nylisoserine (67) does provide an alternative and economic approach (111). N-benzoyl-(2J2, 3S)-3-phenylisoserine (67) is also commonly known as the Taxol side-chain and has been prepared in optically active form using chiral auxiliaries or resolving agents (112). It has been shown that the Taxol side-chain is a conglomerate and can therefore be cheaply and... 

Rao KV, Hanuman JB, Alvarez C et a.I. A new large-scale process for taxol and related taxanes from Taxus brevifolia. Pharm Res 1995 12 1003-10. 

Stasko et al. [8] elaborated two interesting procedures of multimodal TLC for the separation of taxol and related compounds from Taxus brevifolia. For the first procedure, a cyano-modified silica gel plate was developed, in the first dimension, in dichloromethane-hexane-acetic acid (9 10 1) and, in the second dimension, in water-acetonitrile-methanol-tetrahydrofuran (8 5 7 0.1). For the second procedure, a diphenyl-modified silica gel plate was developed, in the first dimension, in hexane-isopropanol-acetone (15 2 3) and, in the second dimension, in methanol-water (7 3). These two methods enabled paclitaxel resolution from cephalomannine, which is impossible on silica gel plates, and at least another 20 compounds. 

Witherup, K.M. Look, S.A. Stasko, M.W. McCloud, T.G. Issaq, H.J. Muschik, G.M. High performance liquid chromatographic separation of taxol and related compounds from Taxus brevifolia. J.Liq.Chromatogr., 1989, 12, 2117-2132 [plants simultaneous baccatin, cephalomannine gradient isocratic]... 

Fuchs, D.A. and Johnson, R.K., Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treat. Rep., 62, 1219, 1978. 

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